Pepitone started doing stand-up comedy in 1978. He took a hiatus from performing stand up comedy and started doing
improv comedy, performing with improv troupe
Chicago City Limits. Described as a "cult favorite", Pepitone is a staple in the
Los Angeles comedy scene. He is known for his regular appearances in the early days of the
WTF with Marc Maron podcast and his
sketch appearances on ''
Late Night with Conan O'Brien and Conan, often playing his recurring role as the "New York City Heckler" in the audience. He has had recurring roles on television programs such as The Life & Times of Tim, The Sarah Silverman Program and Nick Swardson's Pretend Time. His short mockumentary film Runyon: Just Above Sunset'', co-written by Karen Simmons and directed by Troy Conrad, won Best in Show (as well as Best Actor in a Mockumentary) at the L.A. Mockfest as well as Best Comedy Short at the
Burbank Film Festival in 2011. Pepitone often pokes fun at
corporatocracy and has been nicknamed the
Bitter Buddha. Pepitone was a first-round contestant during the first season of
Last Comic Standing. Throughout the late 1990s and early 2000s, Pepitone was a regular sketch performer on ''
Late Night with Conan O'Brien. He has appeared in films such as The Muppets, Old School, School for Scoundrels, and Terri. Pepitone regularly performs stand-up comedy at the Upright Citizens Brigade Theater in Los Angeles. Pepitone has made many guest appearances on comedy programs, including Bob's Burgers, The King of Queens, Chappelle's Show, Malcolm in the Middle, House, Monk, Community, Childrens Hospital, The Eric Andre Show, Happy Endings, Flight of the Conchords, 2 Broke Girls, Whitney, and It's Always Sunny in Philadelphia. Pepitone also appears in the 2012 documentary Alone Up There'', which looks at the craft of stand-up comedy. Pepitone released a
sketch comedy album in 2006 called
The Big Push. His first stand-up album,
A Great Stillness, was recorded at the
Gotham Comedy Club and released in 2011. From 2011 to 2013, Pepitone starred in the 500 episodes of the web comedy series
Puddin'. A documentary about Pepitone's career entitled
The Bitter Buddha was released in 2012 to positive reviews. In the fall of 2013, Pepitone started hosting his own podcast called
Pep Talks after being a member of
The Long Shot podcast for several years. In 2014, he won the September 7 episode of
@midnight. Pepitone appears in the
Adult Swim comedy
Your Pretty Face Is Going to Hell as Eddie, a tortured soul. His stand-up special
For the Masses was released in June 2020. ==Personal life==