There are many facets of the neurobiology of substance use that are distinct in adolescence as compared with adulthood. The adolescent brain is subject to intense subcortical reward processes, but is left with an immature prefrontal control system that is often unable to resist the pull of potentially exciting activities like substance use, even when fully aware of the dangers involved. Peer influences serve only to magnify these effects and foster more sensation-seeking, risky behavior. The unique aspects of neurobiology should be taken into consideration when designing prevention programs and clinical interventions for adolescent substance use disorders.