Demme's first venture into films was the 1992 short "The Bet", a drama about two brothers running a New York deli (the film won awards at the Aspen and Houston film festivals). Shifting to features, Demme's "Who's the Man?" (1993), was a broad "black" comedy starring his MTV co-hosts Doctor Dre and Ed Lover. Loaded with cameos from the world of hip-hop (everyone from Eric B to B Real to B Fine), the film played like a road show version of "Yo! MTV Raps". After helming the acerbic one-man show "Denis Leary: No Cure for Cancer" for Showtime in 1993 and a segment of NBC's "Homicide: Life on the Street" in 1994, Demme directed his first high-profile feature, "The Ref" (1994), a caustic comedy starring slash-and-burn comic Leary as a burglar who takes hostage an extremely argumentative, neurotic couple (Judy Davis and Kevin Spacey). The film earned favorable reviews, despite some lapse in logic born in the editing room, but its incongruous spring release (it was a Christmas movie) hurt its box office and dismayed its director.
Demme's next outing was the buddy film "Beautiful Girls" (1996), a sharply observed slice-of-life tale about the continuity of small-town, working-class existence. The ensemble piece boasted an impressive cast, including Matt Dillon, Lauren Holly, Rosie O'Donnell, Timothy Hutton, Uma Thurman and a St Bernard billed as 'Elle Macpherson', but young Natalie Portman copped the best buzz for her scene-stealing turn as Hutton's precocious 13-year-old neighbor. 1997 saw him act in as well as direct an episode of "Gun" (ABC, executive produced by Robert Altman), and he also helmed that year's "Manhattan Miracle" segment of HBO's "Subway Stories: Tales from the Underground", which teamed him with his uncle Jonathan (who executive produced with actress Rosie Perez), and "Denis Leary: Lock 'n' Load" (HBO). Along with former MTV co-worker and production company partner Joel Stillerman, he then garnered his first feature producing credit on John Dahl's "Rounders" (1998).
Demme executive produced and directed "Monument Ave" (1998), a powerful, ultimately sorrowful meditation on misplaced loyalties and Robin Hood sensibilities. Inspired by and starring Leary (in arguably his best performance to date) as a thirtysomething hoodlum who's never managed to leave behind his working-class Charlestown (Massachusetts) community, it represented another excellent, character-driven ensemble piece for the director, only this time with more bite. Demme picked up his first Emmy as one of the executive producers of HBO's "A Lesson Before Dying" and fulfilled the same role on Gavin O'Connor's gemlike "Tumbleweeds" (both 1999). Though he showed he could helm a big-budget picture when he directed Eddie Murphy and Martin Lawrence in that year's "Life", a prison comedy aging its stars from their 30s to their 90s, he failed to demonstrate the surehandedness of his artistic breakthrough, "Monument Ave". He also served as a creative consultant on the 1999 Fox series "Action", as well as executive producing and helming the show's pilot. His last completed feature was "Blow" (2001) which profiled George Jung (well-played by Johnny Depp), the man who went from small-time marijuana dealer to big-time cocaine importer. The film was criticized in some circles for its sympathetic depiction of someone who was ultimately a drug smuggler.
Demme died after being stricken while playing basketball in a charity tournament on January 13, 2002.