Between 2010 and 2012, Guest appeared both on and off-Broadway in the musical Million Dollar Quartet, playing Johnny Cash.

Guest played Cosmo Cola in Stepsister from Planet Weird (2000).

[citation needed] Guest's starring television roles included Lou Grant (1981–1982) and Knots Landing (1991).

Elsewhere, The Wonder Years, Party of Five, JAG, NYPD Blue, The X-Files, Becker, Life Goes On, House, and Jericho.

[citation needed] Guest has starred on Broadway as Johnny Cash in the musical Million Dollar Quartet, a fictionalized depiction of the only time Carl Perkins, Jerry Lee Lewis, Johnny Cash, and Elvis Presley ever recorded music as a group.