House and the team take on the case of a young woman who, along with her husband, is rescued at sea en route from Cuba in a desperate attempt to see House and get a diagnosis for her illness. During her stay in the hospital, she develops a new symptom: her heart stops,but she keeps talking. Meanwhile, Foreman prepares for his last day at Princeton-Plainsboro Teaching Hospital.
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.
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 (Piper Perabo) named Honey .
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 doctors try to find what\'s wrong with a scam artist who collapses after her brain \"freezes,\" but the case becomes personal for Foreman.
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.
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 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.
The ex-Marine that saved House\'s life, in a dream he had, 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.
House encounters a brain-damaged musical prodigy (Dave Matthews) with inexplicable abilities while the team faces serious concerns about House\'s own health.