The tight-knit Oblong clan lives in Hill Valley, a toxic valley downstream from your typical industrial waste site, which has caused a variety of bizarre physical and emotional abnormalities. At the head of the dinner table is the loving, limbless, tirelessly upbeat patriarch Bob Oblong and his adoring, alcohol-and-tobacco-addicted, bald-but-beautifully-wigged wife Pickles, who frequents the Rusty Bucket bar, owned by transexual Anita Bidet.

The family includes their conjoined twin sons Biff and Chip, who share three legs and three buttocks, but can't seem to agree on anything; sweet, tattling, 4-year-old daughter Beth, sporting a cucumber-like growth sprouting from her head; and youngest son Milo, a one-haired optimist who has every childhood emotional disorder and behavioral problem ever diagnosed. Other members of the family include Bob's mother, Grammy, who's a vegetable; Milo's narcoleptic scottie dog, Scottie; and the chain-smoking family cat, Lucky.

Milo used to go to a special school for "the pathologically high-spirited," but now enjoys his days at "normal" school with fellow valley outcasts including the zaftig, toad-like Helga Phugly; gothic and death-obsessed Creepy Susie; bulbous-bottomed Mikey Butts; and brainy, spitting, lower-jaw-lacking Peggy Weggy. Milo and the gang constantly clash with the Debbies, a giggling gaggle of wealthy, popular, seemingly cloned "hill" girls of the same first name. As far as the Debbies and their parents are concerned, anything that isn't perfect - like them - isn't worthy of their attention. "Normal" school is headed by Principal Davis. Other members of the school staff include Nurse Rench, who has a scary operating contraption in place of her right arm, and the homeroom teacher, Leland. Aside from hanging out in the clubhouse in the Oblongs'back yard, the kids often find themselves hanging out at the local store "A to Zed."

Bob's disregarding boss at Globocide Industries is the aristocratic father, George Klimer. His wife, Pristine, is a Barbie-like, former Debbie, who used to be school friends with Pickles when both girls lived in the hills - before Pickles married Bob and joined the "grotesque" side. Their attractive daughter, Debbie, is leader of the Debbies; and their not-too-bright but popular son Jared, together with his best friend Blaine, is a well-coifed tormentor of the Clubhouse kids.