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Gregory House, M.D., is a maverick medical genius who heads a team of diagnosticians at the fictional Princeton-Plainsboro Teaching Hospital in New Jersey. Most episodes start with a cold open somewhere outside the hospital, showing the events leading to the onset of symptoms for that episode's main patient. The episode follows the team in their attempts to diagnose and treat the patient's illness.

House's nationally-renowned department typically only sees patients who have failed to receive a correct diagnosis, making the patient cases exceptionally complex and subtle. Furthermore, House resists cases that he does not find interesting. The medical cases featured are often rare but realistic, and described by Andrew Holtz, the author of The Medical Science of House, M.D., as "a conglomeration of all the worst things that can happen to people from all over the world, crammed into one little community."

The team arrives at diagnoses using the Socratic method and differential diagnosis, with House guiding the deliberations. House often discounts the information and opinions from his underlings, pointing out that their contributions have missed various relevant factors. The patient is usually misdiagnosed over the course of the episode and treated with medications appropriate to the misdiagnoses. This usually causes further complications in the patient, but in turn helps lead House and his team to the correct diagnosis by using the new symptoms.

Often the ailment cannot be easily deduced because the patient has lied about symptoms and circumstances. House frequently mutters, "Everybody lies", or proclaims during the team's deliberations: "The patient is lying", or "The symptoms never lie." Even when not stated explicitly, this assumption guides House's decisions and diagnoses.

House, M.D., is an Emmy- and Peabody Award–winning American medical drama, which debuted on the FOX network on November 16, 2004. The show was created by David Shore and executive produced by Shore and film director Bryan Singer.