The series takes place at a high school populated entirely by clones of historical figures including Abraham Lincoln, Ghandi, JFK, Joan of Arc, and Cleopatra.
- It is feasible Glenn the Janitor in Clone High is the same Janitor in Scrubs. In the Scrubs episode "My Finale" Janitor tells J.D. his name is Glenn Matthews. In interviews surrounding the Season Eight finale Bill Lawrence said he and Neil Flynn decided Janitor's name would be the same as Flynn's character in the Clone High episode "Litter Kills: Litterally."
- J.D. wears a Clone High t-shirt in "My First Day".
- Michael McDonald (Mike Davis, Mr. Cropper, and the voice of Dr. Toilet on Scrubs) as Gandhi in 13 episodes.
- Christa Miller (Jordan in Scrubs) as Cleopatra in 13 episodes.
- Nicole Sullivan (Jill Tracy in Scrubs) as Joan of Arc and Marie Curie in 13 episodes.
- Donald Faison (Turk in Scrubs) as George Washington Carver, Wally, X-Stream Bob, Toots, Jimi Hendrix, Martin Luther King, Jr., Inmate, and King Kwanzaa over 12 episodes.
- Neil Flynn (Janitor in Scrubs) as Julius Caesar, Carl, Gandhi's Foster Father, Zoo Worker, Buddy Holly, E-CyboPooch, Moses, Pirate, Tux Guy, and Glenn the Janitor over 12 episodes.
- Sarah Chalke (Elliot in Scrubs) as Marie Antoinette and X-Stream Erin over 3 episodes.
- Zach Braff (J.D. in Scrubs) as Paul Revere and X-Stream Mike over 2 episodes.
- Michael J. Fox (Kevin Casey in Scrubs) as Gandhi's Remaining Kidney in one episode.
- John C. McGinley (Dr. Cox in Scrubs) as Creepy Trucker in one episode.
- Bill Lawrence (Van in Scrubs) as Head of the Shadowy Figures.