Wilson still mourns two months after the death of Amber. Needing to make a change in his life, Wilson leaves Princeton-Plainsboro and his best friend, House.
When several people suddenly die without warning, House and the team rush to save others that may have received transplants from the same donor five years prior.
The team takes on the case of a struggling artist who has been painting crazy pictures. His perception has been distorted by his illness, and its threatening to ruin his life.
When House receives word that his father has passed away, he brushes off the news and dismisses the idea of going to the funeral. However, he is soon coerced into going despite his strongest protests.
A woman with whom Thirteen had a one-night stand falls ill and has a seizure at Thirteen's apartment. Thirteen takes the woman to Princeton-Plainsboro where House and the team take her case.
A middle-aged man experiencing blackouts is admitted to Princeton-Plainsboro. With diagnoses ranging from stroke, a concussion to toxins from the consumer products he has been testing for work, House and the team soon find that the man has been experiencing sleepwalking spells.
An agoraphobic man falls ill for no apparent reason, and refuses to leave his home to get treatment. House and the team go to the man's house to figure out what might be wrong, but Cameron takes charge, as she has treated the patient before.
The team takes on the case of a 16-year-old factory manager who fell ill when her lungs suddenly filled with fluid while at work. The teenager informs House and team that she is an emancipated minor living on her own and supporting herself, and has ever since her parents passed away.
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 team takes on the case of a high-profile fitness trainer who collapses while shooting an infomercial. As the team tests her for possible conditions such as exercise-induced asthma, steroid abuse or even a possible vitamin deficiency due to her strict diet, the patient's condition continues to worsen.