The team takes on the case of Derrick, a 19-year-old college student who had a mysterious nosebleed during cheerleading practice, and discovers that his health issues are likely both physiological and psychological. Possibly suffering from schizophrenia, Derrick claims to hear his deceased brother's voice in his head. Meanwhile, Foreman tries a different approach with House. Wilson and House continue to come to terms with Wilson's cancer.

Facing a 6-month jail term and realizing that he won't be there for Wilson at the end, House finds himself examining his entire life while contemplating a dismal future without his best friend. Trapped in a burning building, House must come to terms with his life, choices, personal demons, and future.