Brian Posehn has appeared in a number of comedies such as Seinfeld and Friends.  He had a role in the hit tv series Just Shoot Me. In addition, he has done the voice of Gibbons, a midget, on episodes of Tom Goes to the Mayor. In Aqua Teen Hunger Force, he voiced the Wisdom Cube in the episode "The Cubing".

On the big screen Posehn portrayed a gas station attendant in Dumb and Dumberer and has appeared in the 2003 movie Grind as a customer at Chili 'n Such. He was featured briefly as "himself" alongside Sarah Silverman and Laura Silverman in 2005's Sarah Silverman: Jesus Is Magic. He also portrayed Jimmy Cracker, roadie for Banjo and Sullivan, in Rob Zombie's The Devil's Rejects.

Posehn most recently surfaced on The Showbiz Show with David Spade for a segment called "The Nerd Perspective". In addition he was featured on the documentary series Comedians of Comedy on Comedy Central and Showtime.

In 2006 his first album, Live In: Nerd Rage, was released by Relapse Records. He will voice the character of Murray, in Rob Zombie's upcoming animated film, The Haunted World of El Superbeasto.