A children's novelist tries to kill herself, but is thwarted when she has a seizure. House, a fan of the books, puts her on psych hold but has to deal with a patient that is eager to die rather than be cured. Meanwhile, House worries that he'll lose Cuddy because they have nothing in common.
House and his team make unexpected discoveries about a female patient admitted to the hospital after severe and uncontrollable vomiting; House and Cuddy are forced to face the reservations in their relationship after a visit from a massage therapist.
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.
During a session with Dr. Nolan, House recounts the case of a woman who arrives at the Princeton Plainsboro emergency room with an unexplained illness and no recollection of who she is. While trying to solve the mystery of the woman's illness, House must also help her piece together her identity.
The team takes on the case of an ailing groom-to-be who harbors undisclosed secrets from a previous relationship. As his fiancée tries to get answers to her many questions, a frustrated team winnows down the possibilities. Meanwhile, House spends extra-curricular time with his Princeton Plainsboro colleagues, performing a karaoke rendition of a Gladys Knight & The Pips classic with Foreman and Chase.
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.
House and the team take on the case of Sir William, a "knight" in a closed-off community of men and women living according to the ideals of the High Renaissance. As the team searches the medieval village for environmental factors contributing to Sir William's rapidly deteriorating health, Thirteen and Sir William debate the acts that define honor and loyalty, especially in regard to the "queen" of the community, one of Sir William's most frequent visitors. Meanwhile, Wilson starts over with an ex.
The team takes on the case of a high school senior who inexplicably blacks out during a class field trip. While in the hospital, the patient repeatedly hallucinates. After exhausting myriad ineffective treatments for her mysterious ailments, House attempts one last controversial approach to diagnosing her: monitoring her cognitive patterns and looking for clues. Meanwhile, Taub airs his dirty laundry at work, and Wilson attempts to furnish his condo.