Reilly O'Reilly – The show's main protagonist and antihero, he is paralyzed from the neck down and confined to a wheelchair after getting run over by his future neighbor, Mort Bromberg. The lawsuit against Mort yields him a luxury home in Forest Hills, which he invites his friends to live with him in. For the most part, he is an apathetic and cynical slacker whose main incentives in life include sex with Franny, drinking, and hatching new get-rich-quick schemes that typically end in disaster.
Franny – Reilly's girlfriend. She is a young and voluptuous woman with red hair in a wavy ponytail and pale skin. She appears to be a stereotypical hippie who is into environmental activism, sexuality, New Age spirituality, and refrains from shaving her bodily hair. She also acts as the moral center of an otherwise amoral and chaotic household, as well as a running gag where Franny is a frequent object of lust to Blazer, who repeatedly attempts to hit on her.
Spalding – One of the more stable members of the group, he is Reilly's personal caregiver. He is a homosexual with a well-built physique and is originally from Australia. Although good-intentioned, he is a drama queen who craves attention and allows his lust to get the best of him at times.
Blazer – Having lost his entire body as a result of gambling debts, he has been reduced to a head on a skateboard, which he uses as a means of mobility. He is a crude, ill-mannered, and cantankerous pervert who will go to any length to proposition women for even the most obscene sexual favors. Blazer is also the most nihilistic and amoral of the group, thus making him extremely manipulative and deceptive. As such, he is not above habitually lying to and exploiting his friends for his own personal gain.
Lefty – Formerly a professional masseur, he lost his hands after having mistaken a rabid dog's behind for his client's back and were bitten off. He is an educated and cultured individual that typically finds himself at odds with his housemates, who contrast him personality-wise.
Fontaine – A blind Black man with a gentle and caring demeanour. Due to his blindness and trusting nature, he is frequently taken advantage of by the others in their many escapades. In one episode, it is revealed he has an illegitimate son who is also blind.
Griz – The epitome of unrefined, Griz is a large, disheveled oaf of a man who speaks with an Irish accent and rivals Blazer in his crassness. According to him in one episode, he changes his shirt only once every leap year. He runs a seedy, dilapidated dive bar, infested with rats and cockroaches, that the group frequent for their drinking needs. Griz is perpetually drunk and, as a result, prone to fits of alcoholic rage and extremely poor judgment, the latter of which includes driving severely intoxicated and encouraging the dishonest deeds of others. On the rare occasion Griz is seen sober, he is quick to "fix" this by immediately consuming large quantities of alcohol to return to what he perceives to be his natural state, as he looks upon sobriety with contempt. He also has a sister who is equally repugnant in the way she carries herself.
Mort Bromberg – The man responsible for running Reilly over with his car, crippling him. Feeling guilty, Mort unwittingly buys Reilly an extravagant mansion next to his own, much to the chagrin of his wife, Liz, who despises Reilly and his friends. Despite caring for his wife and doing anything he can to please her, he is often met with Liz's callous indifference to his efforts and even well-being.
Liz Bromberg – Mort's cold-blooded wife. Liz detests Reilly and his friends for the mere fact they are disabled and feels their disadvantaged nature does not jell with the environment of their affluent neighborhood. She initially tried to have the group evicted, but subsequent episodes revolved around her finding some way to take advantage of them.
Deborah – The group's physical therapist who runs a rehabilitation clinic the group frequent for sessions with. She is cheerful and positive, yet addresses the group in a patronizing manner, especially Fontaine, who she speaks to in Ebonics, perhaps assuming he cannot understand standard English.
Sister Butch – A Catholic nun who resides in the cathedral next door to Reilly's house and frequently spies on him and his activities using a pair of binoculars. A harsh and vindictive disciplinarian who believes she is doing God's work, she is often seen attempting to proselytize and force her views down the throats of others. Like Liz Bromberg, Sister Butch is contemptuous of Reilly and his friends, yet, however, does come to his aid on several occasions and even saves his life twice. This is most likely an ulterior motive to persuade Reilly into attending church more regularly.