Comedians who performed on One Night Stand include Susie Essman, Bill Hicks, Bill Maher, Colin Quinn, Dom Irrera, Gilbert Gottfried, Norm Macdonald, Eddie Griffin, Martin Lawrence, D. L. Hughley, Damon Wayans, Larry Miller, Ellen DeGeneres, Charles Fleischer, and George Wallace. This first run of the series ended in 1992, with repeats edited for language and time continuing for years over Comedy Central, a former associate network to HBO.

One Night Stand returned on August 19, 2005. The series aired each Friday at midnight through October 21, 2005, showing a total of ten half-hour stand-up specials. Some of the comedians included are Louis C.K, Jim Norton, Patrice O'Neal, Bill Burr, Bonnie McFarlane, Kevin Brennan, Omid Djalili, Flight of the Conchords, and more. The 2005 version was directed by Linda Mendoza.