Opting to forego a picturesque fall wedding and elope in Las Vegas, Karen hops a plane to "Sin City" with fiance Lyle and faithful friends Will and Jack. After arriving, they bump into superstar Jennifer Lopez who is vacationing and agrees on behalf of Rosario to sing at the ceremony. Meanwhile, Leo returns from Cambodia to meet up with Grace at the wedding, but their reunion is delayed by a freak design accident.
The show takes place in New York City and focuses on Will Truman, a gay man and lawyer, and his best friend Grace Adler, a Jewish woman who runs her own interior design firm.
Also featured are their friends Karen Walker, a rich socialite, and Jack McFarland, a struggling actor/singer/dancer who also has had brief careers as an acting teacher, back-up dancer, cater-waiter, talk-show host and student nurse.