Po powrocie do pracy po postrzale, House bierze 2 przypadki naraz: Richarda, sparaliżowanego po operacji nowotworu mózgu mężczyznę, który wjechał do basenu swoim wózkiem, i Caren, młodą kobietę sparaliżowaną od głowy w dół po sesji jogi. Zespół zauważa wyraźne zmiany House'a w stosunku do pacjentów.

Siedmioletni Clancy zostaje przyjęty do szpitala z krwawieniem z odbytu. Twierdzi, że jest on prześladowany przez kosmitów, którzy chcą go porwać. Chłopiec utrzymuje również, że w jego szyi umieszczono chip, który pozwala kosmitom zlokalizować jego pozycję. Zespół prowadzi różne badania, których wyniki są jednak różne. Największy szok wywołuje na wszystkich wynik badania DNA – Clancy ma 2 różne grupy DNA. Jednak House po dłuższym zastanowieniu postawia diagnozę, która tłumaczy wszystkie objawy.

Nowym pacjentem Housa jest Ezra Powell (Joel Grey), znany pionier badań medycznych, który traci przytomność w swoim laboratorium. Zespół nie jest w stanie wymyslić miarodajnego rozpoznania Ezry, którego stan ciągle się pogarsza. Naukowiec prosi Housa i zespół, aby pomogli mu zakończyć jego życie, ale wszyscy mają swoje własne opinie na temat prośby Ezry, tym bardziej że wyleczenie go ciągle jest możliwe. Tymczasem nastoletnia córka (Leighton Meester) pacjenta House’a z kliniki zaczyna go prześladować.

Do House’a trafia autystyczny chłopak, z bólem w klatce piersiowej. House prosi Cuddy o zmianę nowej wykładziny na starą. Do przychodni przychodzi ponownie napalona nastoletnia córka pacjenta.

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 decides to awaken a comatose patient so he can question the man regarding the family history of his son, who may have a genetic condition and the father is the only living relative. Meanwhile, Wilson confronts House about the stolen prescription pad as Tritter approaches Cameron, Chase, and Foreman in an attempt to divide the team and reveal their loyalties.

An 18-year-old teenager is brought to the hospital after having a heart attack. House reviews the boy's file and believes he has the diagnosis. He then turns the case into a game by sealing his opinion in an envelope and challenging Cameron, Foreman, and Chase to guess House's diagnosis on their own. Meanwhile, Tritter's actions against Wilson continue to strain the oncologist's relationship with House and destroy his ability to practice medicine.

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.

Wilson arranges for House to make a deal with Tritter, but House refuses. Meanwhile, Cuddy cuts House off Vicodin and removes him from the team's case: a 15-year-old little person who entered the hospital with a collapsed lung and anemia.

House splits his time between treating a firefighter for uncontrollable shivering, giving Tritter a piece of his mind, and handling his trial for forging prescriptions.

While House is forced to work full-time in the clinic and deal with a rape victim who insists on confiding with him, Cameron deals with a terminal cancer patient trying to take advantage of her state of mind.

Pewien 16-latek przestaje oddychać podczas pieszczot ze swoją dziewczyną. Lekarze nie są w stanie stwierdzić co jest nie tak, a co gorsza, jego cygańscy rodzice instynktownie nie ufają medykom. Tymczasem Cuddy przydziela miejsce do parkowania dla inwalidów House’a nowej pracownicy szpitala (Wendy Makkena), która jeździ na wózku inwalidzkim, ponieważ jak ujmuje to Cuddy: „osoba, która jest w gorszej kondycji powinna mieć lepsze miejsce”. House nie załatwi tego na leżąco, ale na siedząco – w wózku inwalidzkim.

It's Valentine's Day, and Cuddy has a blind date. Meanwhile, House leaves ER duty to take the case of a child patient named Hannah.

House encounters a brain-damaged musical prodigy with inexplicable abilities while the team faces serious concerns about House's own health.

A famous celebrity photographer suffers from a stroke while being pregnant at her early forties. House and his team have to deal with a great dilemma, save the mother or her unborn child.

On House and Cuddy's flight from Singapore a passenger gets ill and Cuddy suspects an epidemic. At the hospital, Wilson leads the team as they deal with a middle-aged woman suffering from seizures.

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.

The doctors try to find what's wrong with a scam artist who collapses after her brain "freezes," but the case becomes personal for Foreman.

Wilson prepares to transplant bone marrow from Matty to his brother Nick. But when Matty gets sick, the team must cure him as he's the only safe donor. Meanwhile Foreman deals with the consequences of his mistake and House has a battle of wills with his new pet Hector.

The team deals with a 19-year-old college student, while Foreman suddenly and without a reason hands in his resignation. House seems to have already found Foreman's replacement, an attractive nutritionist named Honey.

House treats a 16-year-old chess prodigy who gets everyone on the team annoyed with his behavior. Foreman is upset with House because he thinks his boss sabotaged his job interview with another hospital.

A Cuban couple attempt to get to America by raft... to see House about the wife's heart condition. But when she gets worse House wonders if someone on his staff messed up. Meanwhile Foreman prepares to leave and his departure threatens to shake up the entire team.