A director (Charlize Theron) of an international aid agency in Africa meets a relief aid doctor (Javier Bardem) amidst a political/social revolution, and together face tough choices surrounding humanitarianism and life through civil unrest.

The story follows Joe (Cage), a down-on-his-luck truck driver haunted by the memory of his deceased wife and child. He meets Julie (Potente), a spiritually gifted woman who enlists Joe in a desperate effort to find the lost soul of her comatose daughter, Billie (Mitchell). But the spirit of Joe's dead wife Mary proves stronger, possessing the young woman's body and determined to settle her unfinished business with the living.

In North Carolina's Appalachian Mountains, eighteen-year-old Jacob McNeely is torn between appeasing his meth-dealing kingpin father and leaving the mountains forever with the girl he loves.

A young man struggling for a good life meets a deaf girl from a well-off nearby family, he suddenly sees hope for love, and a better life but only if he can escape the predicament of the streets and the influence of his older sister.