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The leading male protagonist, Bob is an Irish-American white canine, originally from Long Island. He enjoys smoking marijuana and casual sex, even though it sometimes causes conflict with his girlfriend, Charlene, which is why they agreed to an open relationship.
Among other quirks, Bob has the ability to perform fellatio on himself.
Bob's girlfriend, Charlene is an African-American black cat. She shares Bob's love of marijuana and despite his escapades with other women, has strong feelings for him. Charlene was raised Jewish, but has since become agnostic, and is conflicted about her spiritual faith. Moved in with Bob after the death of his second roommate, Tommy. She is also bisexual, and has her own encounters with both male and female castmembers, and even had a girlfriend, Romy, a Jewish lesbian mouse.
Leonard is an African-American black cat, and Bob's best friend. He is one of the most rationally-minded cast members in the strip, although his own choices aren't necessarily perfect in of their own, as he inadvertently caused the break-up of Bob and Charlene's relationship by sleeping with Charlene (although the two later got back together).
Bob's former roommate, a rabbit who served as a Butt Monkey throughout the early segments of the strip due to his stupidity and incompetence, although he occasionally comes across with rational views.
A Hispaniolan Solenodon fortune teller and Hollywood Voodoo practitioner of Haitian decent. Her ancestors were responsible for placing a curse on Bob's ancestor, and she lifts the curse, although this doesn't change the weirdness of the events around him.
A rat Bob dates briefly after Charlene breaks up with him. After Bob and Charlene got back together, Elizabeth began dating Charlene's ex-girlfriend, Romy, even though Beth considered herself straight up until that point. Beth is still in love with Bob, and attempts to gain his interest, even though he's in love with Charlene.
Leonard's girlfriend, a white South African Jewish Aardwolf. Her race results in a lot of Unfortunate Implications when she says things that offend Leonard, whether she realizes it or not.