"Holy Rollers" is inspired by actual events in the late nineties when Hasidic Jews were recruited as mules to smuggle ecstasy from Europe into the United States. Sam Gold (Jesse Eisenberg), a young Hasid from an Orthodox Brooklyn community reluctantly follows the path his family has chosen for him, awaiting a pending arranged marriage and studying to become a Rabbi. A charming neighbor, Yosef Zimmerman (Justin Bartha), senses Sams resistance and propositions him to transport medicine for Jackie (Danny A. Abeckaser), an Israeli dealer, and his girlfriend, Rachel (Ari Graynor).

Sam quickly demonstrates his business skill to his bosses, who instantly take Sam under their wing. Now exposed to the exciting and gritty worlds of Manhattan and Amsterdam nightlife, Sam begins to spiral deeper into their lifestyle, experimenting with ecstasy and then falling for Rachel. As the business grows, Sams double life begins to rip his family apart and the community becomes suspicious of his illegal activities. Sam slowly comes to realize the facade behind the easy money and parties. When he goes on the run, Sam is forced to make a fatal decision that could bring the entire operation crashing down.