This article reviews the recent trend of increasing adolescent substance use, along with other trends of early onset of substance abuse, interrelationships of substance abuse and mental disorders, multiple interrelated risk factors, and the recent emphasis on prevention. A developmental biopsychosocial disease model that integrates research, prevention, and treatment is presented. Predisposing risk factors, substance use initiation and progression, and enabling systems are discussed. Interventions are described along the continuum of treatment and prevention, including an approach of "building the prevention pyramid" for coordinating primary prevention efforts.