All five of the main characters are a clone of a historical figure that met with a violent death: Abraham Lincoln, Mohandas Karamchand Gandhi, and John F. Kennedy were assassinated, Joan of Arc was burned at the stake, and Cleopatra committed suicide by snake bite.
The episode, "Raisin the Stakes" contains multiple subliminal messages. DNA Dan, the school's mascot, appears saying, "Let's Go to the Dark Side". At the PTA meeting, when Principal Scudworth starts talking, a picture of him and the words, "Scudworth is you're favorite character!" flash across the screen. After the first commercial break, where many of the characters are sitting in J.F.K.'s van smoking raisins, a picture of an anthropomorphic raisin smoking a "human doobie" can be seen in one frame. When J.F.K. is sitting in his wheelchair with a broken leg, the message, "I Buried Ponce" flashes across the screen (a reference to the phrase, "I buried Paul", which can allegedly be heard at the end of the Beatles' "Strawberry Fields Forever"). During Abe's hallucination with the real Abe Lincoln, a cartoon re-creation of the famous painting of Joan of Arc flashes across Joan's face as she yells, "Aaa-eee-aa-ee-abe". As Ghandi and the dragon fly over the school at the end, the phrase, "For more information about raisins, consult your local library" flashes across the screen.
In the script for the pilot, Mr. Butlertron was named "Mr. Belvetron" and programmed to take on the characteristics of the sitcom character Mr. Belvedere (1985), which is the reason he calls everyone "Wesley" (most noticeably Ghandi).
In "Raisin the Stakes", J.F.K.'s incoherent mumbling after falling through the skylight is clearly normal speech played in reverse. When recorded and re-reversed, he says: "I am talking backwards, and telling you to watch Clone High, and for us to win an Emmy, I'm saying that backwards, 'cause it's sneaky!"