Will & Grace is the most successful television series with gay principal characters. Despite initial criticism for its particular portrayal of homosexuals, it went on to become a staple of NBC's Must See TV Thursday night lineup, where it was ensconced in the Nielsen Top 20 for half of its network run. Throughout its eight-year run, Will & Grace earned 16 Emmy Awards and 83 nominations.

Will & Grace was filmed in front of a live studio audience (most episodes and scenes) on Tuesday nights, at Stage 17 in CBS Studio Center, a space that totals 14,000 sq. ft. Will and Grace's apartment is on display at the Emerson College Library, having been donated by series creator Max Mutchnick.

In the opening credits, McCormack and Messing are billed together, with top billing alternating between episodes.

Grubbs and Morrison were only credited in episodes they appeared in.

See Supporting characters on Will & Grace for complete list of recurring characters and guest stars.

Will and Grace first met at Columbia University in 1985, living across the hall from one another in a co-ed dorm. They instantly connected and soon began dating. Will then threw a Dorm Party which Jack crashed, and after the party was over Jack accused Will of being in denial about his sexual orientation. After proposing marriage to Grace (as a way to postpone sleeping with her) Will finally came out to her. Grace threw him out of her family's house and they did not speak for a year (Grace having moved off campus), but they accidentally ran into each other again on Thanksgiving the following year (1986) at D'Agostino's supermarket. This meeting spurred a reconciliation and they became best friends. (These events are seen as flashbacks during the third season of the show).

In the pilot episode of the show, Grace was about to get married to her boyfriend Danny. When Will disapproved, she became angry and planned to get married secretly anyway. However on the way to the wedding she realizes that Will was right, and she leaves Danny. Needing an apartment, she moved in with Will in his apartment on the Upper West Side. Will and Grace spend a lot of time with one another as well as with friends Jack McFarland and Karen Walker.

Jack is a flamboyant, gay, struggling stage actor-singer-dancer who, over the course of the show, has a range of jobs including cater waiter, acting teacher, student nurse, retail sales (working for Banana Republic and Barneys), back-up dancer for singers such as Jennifer Lopez and Janet Jackson and TV producer. Karen, an alcoholic multimillionaire, works as Grace's assistant, a job she took to have time away from the home she shares with her husband Stan and his kids, Mason and Olivia. Another character who factored into the early episodes of Will & Grace was Will's client Harlin Polk, played by Gary Grubbs. At first he was given billing in the opening credits with the other four cast members, but interest in his storyline waned, and he was written out of the show early in the second season (Harlin, rather reluctantly, fired Will and hired another lawyer).

The show follows both Will and Grace's attempts to establish romantic relationships without sacrificing their often co-dependent reliance on one another for emotional support. A common joke finds Jack and Karen referring to Will and Grace as married, "non-romantic life partners", or "sexless lovers". At the beginning of the second season Grace moved into her own apartment (across the hall from Will's) in an attempt to put some distance between herself and Will, but then ended up moving back at the beginning of the third season. She moved out again after getting married early in the fifth season, but she moved back in with Will after separating from her husband during Season 6.

Grace had several lovers on the show, portrayed by actors such as Woody Harrelson and Edward Burns. Frequently, her lovers feel frustrated by her relationship with Will, jealous of their closeness, personal jokes, and ability to finish each other's sentences. Eventually she married Leo, played by musician and actor Harry Connick, Jr.. Leo was unusual in that Grace's friendship with Will seemed not to bother him, despite Will's initial dislike of him. Leo in fact often looked to Will in order to help him deal with Grace's neurotic behavior. Furthermore, at one point, when Grace was extremely upset about Leo's upcoming six-month absence, she asked if Will could sleep (platonically) with them, and Leo responded with good humor, saying, "I knew this was going to happen one day." They split in the finale of the show's sixth season after Grace discovered that Leo had had an adulterous affair while working with Doctors Without Borders in Cambodia. In the final season, on a flight to London, Grace meets Leo on the plane where they have sex, resulting in Grace becoming pregnant, which she keeps a secret from him, upon finding that he plans to remarry. In the series finale (May 2006), however, Leo tells a heavily pregnant Grace that he loves her and broke off his engagement. They subsequently raise their daughter, Lilah, together having gotten remarried.