Buscemi is an associate member of the experimental theater company The Wooster Group. Buscemi's character roles include Mr. Pink in Reservoir Dogs, Garland Greene in Con Air, Rockhound in Armageddon, Donny in The Big Lebowski and Carl Showalter in Fargo. Although usually a supporting actor, he has had critical success as a lead actor, particularly in his role as Seymour in Ghost World. Buscemi often plays characters that are neurotic and paranoid. He has appeared in a number of films by the Coen Brothers, wherein he tends to die in a grisly, prolonged or unexpected manner. He frequently provides comic relief in Adam Sandler films such as Billy Madison, The Wedding Singer, Big Daddy and Mr. Deeds. Buscemi played a nemesis to Sandler and Kevin James in the comedy I Now Pronounce You Chuck and Larry. He also has worked with Quentin Tarantino, producer Jerry Bruckheimer, Jim Jarmusch and Robert Rodriguez on various occasions.
In 2003, Buscemi made a brief celebrity guest appearance as himself on the long-running FOX animated television show The Simpsons in the episode "Brake My Wife, Please". In 2004, Buscemi joined the cast of The Sopranos as Tony Soprano's cousin and childhood friend, Tony Blundetto. Buscemi had previously contributed to the show as director of the third season episode "Pine Barrens". He recently appeared in the third episode of Season 6, as a doorman in heaven (portrayed as a country club) in Tony Soprano's dream. He returned to direct the episode " Mr. and Mrs. John Sacrimoni Request", the fifth episode of Season 6.
Buscemi also had a role as Phil Hickle, Ellen's father and older Pete's guidance counselor, in The Adventures of Pete and Pete. He also guest starred in Miami Vice in 1986. Buscemi was rumored to be considered for the role of The Scarecrow in Joel Schumacher's proposed fifth installment of the Batman franchise, Batman Triumphant, before Warner Bros. cancelled the project. He provides the voice of Scamper in the animated Igor, released in 2008.
In the German versions of his films, he is often dubbed by Santiago Ziesmer, known for dubbing the voice of Spongebob Squarepants in Germany (known in Germany as "Spongebob Schwammkopf").

