House's wheels start turning when a pro-cyclist admits to taking performance-enhancing drugs.

House has to work fast when a woman comes in with a life-threatening case of insomnia. Meanwhile Cameron is angry at Foreman for stealing an article she worked on.

House takes the case of a young girl who has been diagnosed with pancreatitis. When he takes her divorced parents to court to force them to allow treatment because they can't agree, the judge awards guardianship of the girl to Cuddy. Meanwhile, Tritter continues his strategy to force House to admit to his drug use by offering one of the team members a deal.

A 6-year-old girl suffers ailments expected in patients much older. Tensions between Chase and Cameron lead House to intentionally assign them to the same tasks, including investigating the young girl's home.

House treats a magician but comes to believe he's faking illness to cover up his own incompetence. Meanwhile, House pits the fellows against each other in his version of an immunity challenge.

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.

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.

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 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 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.

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.

After saving a stranger who fell onto subway tracks, a man suddenly collapses despite appearing to be unscathed; House tries to avoid a dinner with Cuddy and her opinionated mother.

Tension reaches new heights when Cuddy faces sobering news that propels her to reevaluate her priorities. While House is distracted by his concern for Cuddy’s well-being, the team treats a teenage patient whose worsening symptoms and suspicious body scars indicate more than just physical illness.

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.

House and Park treat a patient, Benjamin, who collapsed after making a surprisingly large charity donation, and come to suspect that the altruistic behavior is a symptom of a deeper disorder. When the patient offers to donate an organ for another patient, the doctors must convince Dr. Adams to help them confirm whether Benjamin is in his right mind or not.

House's green-card wife, Dominika, will return in order to prove to the proper authorities that she and House are actually married. This in turn will lead to a crash course in which both will learn a little something about love and marriage.

House and the team take on the case of a man who starts tearing blood. Meanwhile, House is interviewing for a new favorite hooker, since his current favorite, Emily, has decided to get married and leave the business. Desperate for Emily "companionship," House teams up with his "wife" Dominika to sabotage Emily's budding relationship.