César Borgnoli, un concessionnaire de voitures italiennes vivant largement au-dessus de ses moyens, est au bord de la ruine. Sa sœur Alex, qui vit en couple avec sa compagne Kim, lui propose de sauver le garage familial en lui mettant un marché en mains.
Henry Petosa and Freddy Ace are identical twins living in the fictional city of Empire with no knowledge of each other, separated at birth and given up for adoption.
The film opens with a woman leaving a bassinet on the porch of a fancy home; the baby, Junior, promptly pees on the woman who picks him up. From there, he is repeatedly discarded at various homes throughout many years by guardians who have grown tired of his destructive behavior—which includes throwing a rattle at the window, giving a cat soap to eat, using a vacuum cleaner to suck up the fish tank, and demolishing a mobile home with a bulldozer in retaliation for his favorite toys being stepped on—until he is eventually deposited at a Catholic orphanage, where he continues to wreak havoc on the strict nuns.
In Harlem, 10-year-old Annie Bennett lives in foster care with several other girls in the care of the cruel Colleen Hannigan. She spends each Friday waiting outside the restaurant Domani's where she believes her parents will return to collect her.
In California, John Netherwood (Keith Carradine) and his wife Leann Netherwood (Daryl Hannah) are fugitives who are wanted for murder. They have a 6-year-old daughter named Janie (Julia Devin).
Virginia congressman Gene York (Michael Woods) and his attorney wife Karen (Faye Grant), after numerous failed attempts to have children, go to a nun-owned orphanage where they adopt a child that they name Delia from a nun named Sister Yvonne. At first, other than Delia scratching Karen and the later heart attack of the preacher overseeing her baptism, all seems normal. But seven years later, after the Yorks adopt a rottweiler that they name Ryder, Delia (Asia Vieira) starts to display the traits and personality of an increasingly violent and manipulative sociopath. Furthermore, as the family doctor Hastings reveals that she is going through puberty, strange events begin to occur around Delia, including the death of the father of a boy whom she terrorized. Jo Thueson, a New Age practitioner hired by the Yorks as a nanny to help while Gene runs for the Senate, senses something suspicious about Delia after finding her healing crystals blackened by the girl's touch.
In 1986, young Darius Foxx witnessed his mailman father shoot his wife and her secret lover, then himself. Eighteen years later, Darius becomes the new mailman of Smithfield, cryptically informing the townspeople that his predecessor is "out of town" for an indeterminate amount of time.