Adolescent addiction is widely recognized as a serious problem that requires close monitoring and more effective interventions. While fewer adolescents are trying drugs, presumably due to extensive anti–drug education and media campaigns, many are already addicted and unlikely to quit without professional assistance. Pharmacotherapy is a potential means of improving clinical outcome in addicted adolescents, particularly in light of the scientific evidence that supports a strong neurobiological basis for addiction. In fact, research in adult subjects has identified effective treatments for opioid, nicotine, and alcohol dependence, and several promising compounds are under investigation for cocaine dependence. Unfortunately, few medication trials have included adolescent subjects so little is known about efficacy, optimal dosage, and tolerability in the adolescent population. Clinicians often face the difficult task of differentiating transient drug abuse from the early stages of addiction in adolescents. While some are very vulnerable, based on genetic, environmental, and psychological characteristics, most adolescents who experiment with drugs do not become addicted. The diagnostic criteria for addiction include the presence of tolerance or withdrawal, the use of more drugs than intended, unsuccessful efforts to quit, excessive time spent obtaining drugs, and continued use in the face of negative consequences. Not all of these criteria are required to make the diagnosis, and the quintessential feature of addiction involves losing control over drug use and drug–seeking behaviors. Since adolescents are usually reluctant to disclose their drug use, the diagnosis is often based on collateral information from the family, school, and laboratory. Since adolescents commonly abuse more than one drug, clinicians should be familiar with all of the commonly abused agents discussed in the following pages. In addition, co–occurring psychiatric and medical disorders, beyond the scope of this review, should be identified with a comprehensive evaluation and expeditiously treated.