Jack Sadelstein, a successful advertising executive in Los Angeles with a beautiful wife and kids, dreads one event each year: the Thanksgiving visit of his twin sister Jill. Jill's neediness and passive-aggressiveness is maddening to Jack, turning his normally tranquil life upside down.

Dr. Gregory House, a drug-addicted, unconventional, misanthropic medical genius, leads a team of diagnosticians at the fictional Princeton–Plainsboro Teaching Hospital in New Jersey.