House believes a woman is trying to kill her husband and tries to find the proof to confirm his suspicions. When Wilson moves in with House after separating from his wife, he learns Wilson is a great cook.

House takes the case of a young woman who has been rushed to the hospital with problems breathing and severe stomach pain after she and her husband were robbed. After her husband collapses, the team believes the couple's illnesses are related. Meanwhile, Michael Tritter, a clinic patient, causes problems for House that could have serious ramifications.

The team encounters logistical problems while trying to run tests on a 600-pound man due to his extremely large size. Meanwhile, House spends the night in jail after being arrested by Detective Tritter for various charges, including resisting arrest.

House and his staff must deal with a teenage Gypsy boy suffering from inexplicable respiratory distress. However, House has bigger issues on his mind: Cuddy has given away his handicapped spot.

The ex-marine that saved House's life, in a dream he had the day before, is admitted in the hospital with symptoms resembling Gulf War Syndrome. While House is busy dealing with his own health issues, and Chase and Cameron are too busy with each other, the ex-marine gets worse.

A mother's sudden paralysis during a indoor rock-climbing incident leaves her daughter injured, and House's new team looking for a cure. Meanwhile, House organizes his new recruits' Secret Santa gift exchange... with a few twists of his own.

House is convinced one of the actors on his favorite soap opera “Prescription Passion” has a serious medical condition after observing his symptoms on television. House decides to intervene and take matters into his own hands, but both the actor and House's own team dismiss House’s assessment and do not believe there is anything wrong with him.

A bus accident leaves House with serious head trauma and partial amnesia. He comes to believe that a patient on the bus had a life-threatening disease and struggles to recall who it was, and what they had.

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.

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.

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.

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.

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.

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.

House and Cuddy are exploring the ramifications of those feelings and attempting to make a real relationship work. Meanwhile, due to a colleague's illness, Princeton Plainsboro is left without a neurosurgeon on site, threatening the hospital's accreditation as a Level 1 Trauma Center. As the team attempts treatment to get their sick colleague back to work, they discover there is more to the illness than they originally suspected and turn to House for direction. Instead, House remains elusive, leaving the team on its own.

The team treats a professional bull rider who is attacked by a bull. The team must determine the causes behind the patients disappearing symptoms and seizures while taking House's advice from outside the hospital as he attends to issues unrelated to the case. Meanwhile, Masters develops a crush on the patient.

Thirteen has been in prison for the past year, but the real mystery for House is what she did to get there. At the hospital, the team treats a science teacher suffering from severe respiratory illness. Taub tries to get back into the dating scene, but winds up retreating to his old habits.

Over the years, during the course of performing autopsies at Princeton-Plainsboro, Dr. Peter Treiber has often identified mistakes made by physicians that caused the patient's death. These observations have left him questioning the skills of nearly all the doctors on staff... all, that is, except House. When he falls ill, he demands that only House make medical decisions concerning his care. Unfortunately, House and Wilson have taken off on an impromptu road trip without telling anyone, leaving the team to fend alone and lie to their patient to make him believe that House is the guy calling all the shots.

Facing a 6-month jail term, and the realization that he won't be there for Wilson at the end, House finds himself examining his entire life while contemplating a dismal future without his best friend.