Policemen Bonaro and Madigan lose their guns to fugitive Barney Benesch. As compensation, the two NYC detectives are given a weekend to bring Benesch to justice. While Bonaro and Madigan follow up on various leads, Police Commissioner Russell goes about his duties, including attending functions, meeting with aggrieved relatives, and counseling the spouses of fallen officers.

The nineteen years old Catholic college girl Emily Rose (Jennifer Carpenter) dies a couple of days after being submitted to an exorcism carried out by her parish priest, Father Moore (Tom Wilkinson). Emily believed she was possessed by six demons, and although authorized by Emily and he parents, Father Moore is accused of negligent homicide, since he had suggested Emily to interrupt the use of medications for epilepsy. In order to avoid a scandal, the Archdiocese hires the successful, ambitious and agnostic lawyer Erin Bruner (Laura Linney), and the prosecution assigns the religious prosecutor Ethan Thomas (Campbell Scott). Along the days, there is a battle between science and religion in the court.

Rachel Keller is a journalist investigating a videotape that may have killed four teenagers (including her niece). There is an urban legend about this tape: the viewer will die seven days after watching it. If the legend is correct, Rachel will have to run against time to save her son’s and her own life.