In 2004, David Shore and Paul Attanasio, along with Attanasio's business partner Katie Jacobs, pitched the series (untitled at the time) to Fox as a CSI-style medical detective program, a hospital whodunit in which the doctors investigated symptoms and their causes; the main character would be loosely based on Arthur Conan Doyle's "Sherlock Holmes". Attanasio was inspired to develop a medical procedural drama by The New York Times Magazine column "Diagnosis", written by physician Lisa Sanders, who is an attending physician at Yale–New Haven Hospital (YNHH); the fictitious Princeton–Plainsboro Teaching Hospital (PPTH, not to be confused with the University Medical Center of Princeton at Plainsboro) is modeled after this teaching institution. Fox bought the series, though the network's then-president, Gail Berman, told the creative team, "I want a medical show, but I don't want to see white coats going down the hallway". Jacobs has said that this stipulation was one of the many influences that led to the show's ultimate form.

After Fox picked up the show, it acquired the working title Chasing Zebras, Circling the Drain ("zebra" is medical slang for an unusual or obscure diagnosis, while "circling the drain" refers to terminal cases, patients in an irreversible decline). The original premise of the show was of a team of doctors working together trying to "diagnose the undiagnosable". Shore felt it was important to have an interesting central character, one who could examine patients' personal characteristics and diagnose their ailments by figuring out their secrets and lies. As Shore and the rest of the creative team explored the character's possibilities, the program concept became less of procedure and more focused upon the lead role. The character was named "House", which was adopted as the show's title, as well. Shore developed the characters further and wrote the script for the pilot episode. Bryan Singer, who directed the pilot episode and had a major role in casting the primary roles, has said that the "title of the pilot was 'Everybody Lies', and that's the premise of the show". Shore has said that the central storylines of several early episodes were based on the work of Berton Roueché, a staff writer for The New Yorker between 1944 and 1994, who specialized in features about unusual medical cases.

Shore traced the concept for the title character to his experience as a patient at a teaching hospital. He recalled: "I knew, as soon as I left the room, they would be mocking me relentlessly [for my cluelessness] and I thought that it would be interesting to see a character who actually did that before they left the room." A central part of the show's premise was that the main character would be disabled in some way. The original idea was for House to use a wheelchair, but Fox rejected this. Jacobs later expressed her gratitude for the network's insistence that the character be reimagined—putting him on h…

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Gregory House, M.D., often construed as a misanthropic medical genius, heads a team of diagnosticians at the Princeton–Plainsboro Teaching Hospital in New Jersey. The series is structured around a central plot with some supporting secondary stories and narratives that cross over seasons. Most episodes revolve around the diagnosis of a primary patient and start with a cold open set outside the hospital, showing events ending with the onset of the patient's symptoms. The typical episode follows the team in their attempts to diagnose and treat the patient's illness, which often fail until the patient's condition is critical. They usually treat only patients whom other doctors have not accurately diagnosed, and House routinely rejects cases he does not find interesting.

Typically, the patient is misdiagnosed at least once which usually causes further complications, but the nature of the complications often provides new evidence which helps them diagnose the patient correctly. House often tends to arrive at the correct diagnosis seemingly out of the blue, often inspired by a passing remark made by another character. Diagnoses range from relatively common to very rare diseases.

The team faces many diagnostic difficulties from patients' concealment of symptoms, circumstances, or personal histories, so House frequently proclaims during the team's deliberations, "The patient is lying", or mutters "Everybody lies"; such an assumption guides House's decisions and diagnoses and makes housebreaking a routine tactic. Because many of his hypotheses are based on epiphanies or controversial insights, he often has trouble obtaining permission for medical procedures he considers necessary from his superior, who in all but the final season is hospital administrator Dr. Lisa Cuddy. This is especially the case when the proposed procedures involve a high degree of risk or are ethically questionable. Frequent disagreements occur between House and his team, especially Dr. Allison Cameron, whose standards of medical ethics are more conservative than those of the other characters.

Like all of the hospital's doctors, House is required to treat patients in the facility's walk-in clinic. His grudging fulfillment of this duty, or his creative methods of avoiding it, constitute a recurring subplot, which often serves as the series' comic relief. During clinic duty, House confounds patients with unwelcome observations into their personal lives, eccentric prescriptions, and unorthodox treatments. However, after seeming to be inattentive to their complaints, he regularly impresses them with rapid and accurate diagnoses. Analogies with some of the simple cases in the clinic occasionally inspire insights that help solve the team's case.

A significant plot element is House's use of Vicodin to manage pain, caused by an infarction in the quadriceps muscle of his right leg five years before the show's first season, which also forces him to use a cane. In the first-season 11th episode "Detox", House admits he is addicted to Vicodin but says he does not have a problem because the pills "let me do my job, and they take away my pain". His addiction has led his colleagues Cuddy and Dr. James Wilson to encourage him to go to drug rehabilitation several times. When he has no access to Vicodin or experiences unusually intense pain, he occasionally self-medicates with other narcotic analgesics such as morphine, oxycodone, and methadone. H…

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House received largely positive reviews on its debut; the series was considered a bright spot amid Fox's schedule, which at the time was largely filled with reality shows. Season one holds a Metacritic score of 75 out of 100, based on 30 reviews, indicating "generally favorable" reviews. Matt Roush of TV Guide said that the program was an "uncommon cure for the common medical drama". New York Daily News critic David Bianculli applauded the "high caliber of acting and script". The Onion's "A.V. Club" approvingly described it as the "nastiest" black comedy from FOX since 1996's short-lived Profit. New York's John Leonard called the series "medical TV at its most satisfying and basic", while The Boston Globe's Matthew Gilbert appreciated that the show did not attempt to hide the flaws of the characters to assuage viewers' fears about "HMO factories". Variety's Brian Lowry, less impressed, wrote that the show relied on "by-the-numbers storytelling, albeit in a glossy package". Tim Goodman of the San Francisco Chronicle described it as "mediocre" and unoriginal. Mikhail Varshavski, a Russian-American Osteopathic Doctor, reviewed the medical content of House on his YouTube channel. According to Varshavski, the medical information presented on the show was usually fundamentally accurate though often highly exaggerated for dramatic effect, but he described Gregory House's tendency to quickly use invasive tests and procedures as outside the medical mainstream.

General critical reaction to the character of Gregory House was particularly positive. Tom Shales of The Washington Post called him "the most electrifying new main character to hit television in years". The Pittsburgh Post-Gazette's Rob Owen found him "fascinatingly unsympathetic". Critics have compared House to fictional detectives Nero Wolfe, Hercule Poirot, and Adrian Monk, and to Perry Cox, a cantankerous doctor on the television show Scrubs. One book-length study of the series finds a powerful kinship between House and another famous TV doctor, Hawkeye Pierce of M*A*S*H. Laurie's performance in the role has been widely praised. The San Francisco Chronicle's Goodman called him "a wonder to behold" and "about the only reason to watch House".

Critics have also reacted positively to the show's original supporting cast, which the Post's Shales called a "first-rate ensemble". Leonard's portrayal of Dr. Wilson has been considered Emmy Award worthy by critics with TV Guide, Entertainment Weekly, and USA Today. Bianculli of the Daily News was happy to see Edelstein "was finally given a deservedly meaty co-starring role". Freelance critic Daniel Fienberg was disappointed that Leonard and Edelstein have not received more recognition for their performances.

Reaction to the major shifts of season four was mixed. "With the new crew in place House takes on a slightly more energized feel", wrote Todd Douglass Jr. of DVD Talk. "And the set up [sic] for the fifth season is quite brilliant." The Star-Ledger's Alan Sepinwall wrote, "The extended, enormous job audition gave the writers a chance to reinvigorate the show and fully embrace Laurie's comic genius". Mary McNamara of the Los Angeles Times, on the other hand, took issue with the developments: "the cast just kept getting bigger, the stories more scattered and uneven until you had a bunch of great actors forced to stand around watching Hugh Laurie hold the show together by the sheer force of his will". USA Today's Robert Bianco cheered the season finale: "Talk about saving the best for last. With two fabulous, heartbreaking hours ... the writers rescue…

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