Adolescents as young as 12 to 14 years of age are engaging in substance use [16]. Those who use substances are at risk for immediate and future consequences that affect morbidity and mortality. The theoretical models of substance use in adolescents provide a framework for understanding risk and protective factors. These risk and protective factors are pertinent to all contexts, including the individual traits, interpersonal relationships, and greater society. Knowledge of these factors should help the clinician in assessment of the individual adolescent. Knowledge of these factors also should help the clinician provide appropriate interventions. In the case of primary prevention, clinicians can advocate for families and communities to teach children how to be more goal-oriented, insightful, and in tune with their cultures and beliefs. Parents also can be encouraged to set clear limits, monitor their adolescents' behaviors, be good role models, and provide a loving and supportive environment. Advocacy to address some of the societal factors that are less easily changed also has its place. Addressing media portrayal of drug use, availability of substances, and poverty would have a broad impact on the problem of adolescent substance use and would help to improve the health status of many adolescents in the United States.