In the aftermath of personal tragedy, Wilson resigns from the hospital... and from his friendship with House. Meanwhile, Thirteen struggles with her personal medical problems while helping treat an executive assistant with a similar situation to her own.

The team deals with an organ donor whose organs prove fatal, and the two surviving patients. Meanwhile, House hires a private detective to spy on Wilson, but hears a few things about himself that he'd rather not.

A painter's undiagnosed illness affects his work, and House and his team must look at the man's paintings to determine what's wrong with him.

While en route to his father's funeral, House must help the team with a differential diagnosis on a young Chinese girl who has collapsed under mysterious circumstances.

Thirteen brings her one-night stand to the hospital after the woman has a seizure. However, the woman admits she slept with Thirteen just so she could get to House and have him diagnose her condition. Meanwhile, House continues to pay Lucas to spy on Wilson.

An ailing man suffers from blackouts and sleepwalks, leading the team to wonder if his sleepwalking is a symptom, or how the man is becoming exposed to something else. When the man's daughter grows ill as well, the team must provide a diagnosis before both die. Meanwhile, Cuddy adopts a newborn but when the birth mother displays a rash, she has to make a decision between putting the mother or daughter at risk.

The team must treat an agoraphobic who refuses to leave his house, and have to work around Cuddy, who is less than thrilled at having hospital equipment relocated. Meanwhile, House is plagued by an itch, and Cameron and Chase have relationship issues.

While Foreman takes on a pediatric case on his own, the rest of the team deals with a 16-year-old factory manager and emancipated minor who collapses at work. When Foreman's patient takes a turn for the worse, he's forced to question whether he can deal with the situation on his own, or if he needs House's help.

A gun-wielding man from the waiting room at the Princeton-Plainsboro clinic takes House, Thirteen and several patients from the waiting room hostage in Cuddy's office. The man claims to be sick with a long undiagnosed illness and demands medical attention from the best doctor in the hospital, threatening to kill any hostages necessary along the way.

The team takes on the case of a fitness guru on an all-natural diet who collapsed while filming a video. Meanwhile, Foreman conducts Huntington's Disease drug trials and Thirteen signs on as a subject, Cuddy is forced to move into House's office, and Kutner uses House's name to run an online medical-advice website.

House and his team deal with a bullied girl who collapses during her school's Christmas program. Meanwhile, Foreman and Thirteen grow closer during the Huntington's disease drug trials, House gives a patient a gift, the staff wonder who gave House a special gift, and Cuddy gets an unexpected gift.

House and the team try to diagnose a man living with severe, chronic pain; Thirteen and Foreman explore their complicated relationship; Cuddy discovers that caring for her baby leaves her with little time to run the hospital.

Cuddy decides to spend more time at home to take care of her newly adopted baby and passes some of her day-to-day responsibilities off to Cameron, including supervising House. Cameron is forced to play House’s games and becomes involved in a power struggle as he and the team take on the case of a Special Education teacher who collapsed after spitting up blood in the middle of class. As House tests Cameron’s tolerance for his extreme measures, the patient continues to fall ill and House insists the teacher’s seemingly inherent goodness is actually a pathology.

House and the team take on the case of a woman who collapsed in the middle of a cooking class, and they soon learn she is a highly-renowned cancer researcher who recently gave up her entire career in order to pursue her own personal happiness. Though the team struggles to understand how the woman could give up saving lives for the sake of her own contentment, each grapple with the pursuit of happiness (or lack thereof) in their own lives. As the patient’s condition continues to worsen, so does Thirteen’s as she begins to suffer serious and life-threatening reactions to the experimental Huntington’s Disease clinical trial. Meanwhile, Cuddy attempts to make House’s life miserable for him in retaliation for his part in her own unhappiness.

When a priest who runs a homeless shelter sees a bleeding Jesus hovering at his doorstep, he is admitted to the ER. House takes on the case as a distraction for the team while he confronts Foreman and Thirteen about their relationship. The team soon learns the priest had been involved in a molestation scandal that caused him to lose his faith. However, just as they are about to dismiss his case, the patient’s condition takes a drastic turn for the worse, and House grapples with his past and his belief

A patient with both male and female DNA has the team stumped. Meanwhile, House starts acting nicely, raising Cuddy's and Wilson's suspicions that something is terribly wrong.

House and the team take on the case of Nick, a book editor who loses his inhibitions. The team realizes Nick has frontal lobe disinhibition, which causes him to speak his mind having no control over what he says and making him just like House. Meanwhile, House suspects Wilson and Taub are keeping something from him.

Morgan works in a nursing home with a pet cat who only sleeps next to people if they are about to die - and does so with alarmingly accuracy. When it seems the cat has predicted her own death, Morgan, convinced she is about to die, fakes a seizure in order to get to House to have him diagnose her before it’s too late.

A man awakens in New York after a bicycle accident unable to move or communicate in any way. House, himself injured in a motorcycle mishap, occupies the hospital bed next to Lee and quickly annoys the doctors treating them both by insisting that Lee has “locked-in” syndrome.

Charlotte, an older woman who has spent the last six months taking care of her dying husband Eddie, is rushed to Princeton Plainsboro after collapsing from respiratory failure. The couple becomes a double mystery for the team when Eddie begins to improve as Charlotte’s condition worsens. The previously unthinkable becomes real when it seems that Charlotte will die before Eddie, and the team will be forced to make a difficult decision.

Cameron postpones her vacation with Chase in order to ask House to accept the case of an environmental radical who collapsed at a protest with unexplainable symptoms. Although suspicious of her motives, House agrees. Since she pushed him to take the case so emphatically, House forces Cameron to take the lead and run many of the tests on the patient. Meanwhile, House is unsure of Wilson’s new healthy diet.

The team takes on the case of a deaf 14-year-old named Seth who collapsed after he started “hearing” explosions while competing in a wrestling match. When the team tries to test him for seizures, Seth loses vision in one eye, complicating House’s bunk theory of “Exploding Head Syndrome.” As his condition worsens, the team has an ethical disagreement about the patient and his mother’s adamant decision to forego cochlear implants to supplement his hearing. When the prospect of giving Seth the ability to hear for the first time in his life arises, House and the team are faced with a resounding decision. Meanwhile, House’s lack of sleep starts to play tricks on his mind, but he finds his insomnia may be a gift instead of a burden

House and the team take on the case of a ballerina whose lungs collapse in the middle of a performance. When the treatment causes her skin to fall off, the dancer faces not only the prospect of never dancing again but also of dying an agonizing death. The team must use their imaginations to carefully choreograph ways to test and treat her delicate body without killing her. Meanwhile, House continues to suffer from what he thinks is insomnia, and he is willing to go to desperate measures to cure it.

House and the team are intrigued by Scott, a man whose left brain and right brain operate independently, leaving him with two distinct personalities and no control over some of his actions. As the two sides of Scott’s brain struggle for dominance, his warring personalities make it increasingly difficult for the team to figure out what is causing the unique problem. The team is forced to use some unusual methods to get him to cooperate with their necessary testing. Meanwhile, when House refuses to make an appearance in the clinic, Cuddy takes an unconventional approach to force House to make up the time with a particular patient.

House engages in a battle of wits and wills against the attending physician in charge of his detox program. When he starts to lose, House resorts to blackmail to gain the upper hand.

House asks Alvie to help him uncover incriminating information about Dr. Nolan that would allow him to blackmail his way out of the treatment center and convinces Lydia to loan him her car to sneak out a delusional patient in an attempt by House to undermine Dr. Nolan's course of treatment. But when devastating events ensue, House is humbled into reluctantly accepting help.

House returns home to Princeton where he continues to focus on his recovery, but surprises Cuddy with the news that he's making a big change in his life. Meanwhile, the team is unable to diagnose a loud-mouthed video game creator who posts each new symptom on the internet and opts for treatments suggested by the online community rather than by the doctors, and Foreman angles for House's job, but the pressure to solve the case creates tension in his relationship with Thirteen.

When a controversial African politician falls ill, he is brought to Princeton Plainsboro for treatment. The team struggles with whether to help a merciless dictator being subpoenaed for crimes against humanity in his country. Meanwhile, Wilson tries to make peace with a feuding neighbor, but House’s prying exacerbates the problem.

A wealthy businessman brings his teenage son, who is suffering from inexplicable stomach pains, to Princeton Plainsboro and insists on having Dr. House handle the case. The father of the patient believes the karmic penalty of his financial success is that he is victim to personal tragedy, and that the answer to his son's medical mystery lies in a reverse of fate rather than medical treatment. Meanwhile, Foreman and Chase prepare to present information on the Dibala case.

A dying patient insists that he has the same disease affecting his heart that killed his father and grandfather at the age of 40. Meanwhile, House discovers that he has a hearing problem while trying to duck student rounds.

After a wild night out, a teenage girl is brought to Princeton Plainsborough with severely swollen appendages. The team must work to diagnose the young girl, who is less than honest about what happened the night she fell ill. As her condition worsens, she becomes unable to distinguish fact from fiction. Meanwhile, Cuddy, Wilson and House spend a weekend away from the hospital to attend a medical conference, but things don’t go as planned when House’s private investigator, Lucas returns.

After House’s medical license is reinstated, he reclaims his role as Head of Diagnostics in time to treat Hank Hardwick, an adult film star admitted to Princeton Plainsborough for pulsating eye pain. Meanwhile, Cuddy is reminded that Princeton Plainsborough is not conducive to healthy personal relationships.

On the eve of Thanksgiving, House and the team take on the case of James Sidas, an exceptionally brilliant physicist and author who traded his successful career for a job as a courier. For the ailing patient, intelligence is a miserable burden that has prompted depression and addiction, and this, coupled with a myriad of strange symptoms, nearly stumps the team. Meanwhile the doctors at Princeton Plainsboro wrestle with strained personal relationships.

When an old friend and former patient of Wilson’s exhibits paralysis in his right arm, Wilson puts himself on the case. House wagers Wilson that the patient’s symptoms are attributed to new cancer cells. Wilson accepts even though he is reluctant to believe the cancer has returned. With the help of the team, Wilson works to diagnose the patient more optimistic results, but when things take a turn for the worse, Wilson must address his inability to separate patient from friend. Meanwhile, Cuddy seeks advice in her search for real estate.

When drug dealer Mickey mysteriously collapses while negotiating a sale, his partner-in-crime, Eddie, accompanies him to Princeton Plainsboro for treatment. But with a major deal pending, Mickey is not forthcoming with the necessary personal information the team needs to treat him. As Mickey's condition worsens, the team resorts to old-fashioned detective work to solve the case. Meanwhile, House and Wilson compete for the affection of a new neighbor, and Chase, Thirteen and Taub attempt to play a practical joke on Foreman.

The team takes on the case of Valerie, an attractive female executive experiencing random episodes of excruciating pain. House agrees to take the case based on Valerie’s looks, and while treating her, the men on the team are charmed by Valerie’s beauty and personality, with Thirteen looking beyond the superficial to try to discover a link to her illness. Meanwhile, House uncharacteristically attempts to alleviate his conscience by reaching out to a former medical school colleague he wronged.

House and the team rush to treat an ailing college football star in time for the patient to compete in NFL tryouts. But when the patient experiences an onslaught of varied and unusual symptoms, the team has trouble reaching a consensus on how to effectively treat him in time. Meanwhile, Foreman’s brother Marcus makes a surprise visit to the hospital.

During a day in the life of Princeton Plainsboro's Dean of Medicine, Dr. Lisa Cuddy, the inner workings of the hospital are seen through her eyes. This day proves to be especially trying as Cuddy wrestles with myriad hospital issues and staff disputes that test her perseverance and skills as an administrator, all while juggling issues in her personal life.

House and the team take on the case of an avid blogger admitted with sudden bruising and bleeding. From her hospital bed, the patient blogs about her symptoms, doctors and prospective diagnoses to her dedicated band of followers and solicits their advice on a course of treatment. Such openness leads the team to contemplate the value of privacy, especially after House and Wilson uncover secrets from one another 's past. Meanwhile, Chase is coaxed into testing out the dating scene.

The team takes on the case of a high school senior who inexplicably blacks out during a class field trip. While in the hospital, the patient repeatedly hallucinates. After exhausting myriad ineffective treatments for her mysterious ailments, House attempts one last controversial approach to diagnosing her: monitoring her cognitive patterns and looking for clues. Meanwhile, Taub airs his dirty laundry at work, and Wilson attempts to furnish his condo.

This episode has five storylines: When the hospital is sent into lock-down mode due to a missing infant, all of the doctors must remain where they are, leaving Foreman and Taub in the file room, Wilson and Thirteen in the cafeteria playing truth or dare, House in a room with a patient, and Chase with his soon-to-be ex-wife, Cameron, as Cuddy tries to help police locate the infant. This episode is one of the show's rare instances when no medical mystery is presented, though House still deals with his "patient of the week".

House and the team take on the case of Sir William, a "knight" in a closed-off community of men and women living according to the ideals of the High Renaissance. As the team searches the medieval village for environmental factors contributing to Sir William's rapidly deteriorating health, Thirteen and Sir William debate the acts that define honor and loyalty, especially in regard to the "queen" of the community, one of Sir William's most frequent visitors. Meanwhile, Wilson starts over with an ex.

House and the team take on the case of a woman Julia, who is in an open marriage and becomes ill during a date with her on-the-side boyfriend. As perplexing as the case is, Julia's happy and healthy, yet polygamous relationship is equally baffling to the team. Meanwhile, House tests Wilson's relationship with Sam.

The team takes on the case of an ailing groom-to-be who harbors undisclosed secrets from a previous relationship. As his fiancée tries to get answers to her many questions, a frustrated team winnows down the possibilities. Meanwhile, House spends extra-curricular time with his Princeton Plainsboro colleagues, performing a karaoke rendition of a Gladys Knight & The Pips classic with Foreman and Chase.

During a session with Dr. Nolan, House recounts the case of a woman who arrives at the Princeton Plainsboro emergency room with an unexplained illness and no recollection of who she is. While trying to solve the mystery of the woman's illness, House must also help her piece together her identity.

Cuddy, House and members of the team join forces with a search-and-rescue team to provide much-needed medical attention at the scene of an emergency.