Substance use in adolescence is common, but not all use indicates a substance use disorder. The primary care provider has an essential role in screening for substance involvement, assessing the level of substance use and its impact on function, and engaging in a brief intervention to encourage and support behavioral change related to substance use. This article summarizes the literature on adolescent vulnerability to substance use disorders and their impact on adolescent health and well-being. Practical concrete suggestions for approaches to screening, brief interventions, and referral to treatment provide a stepwise approach to adolescent substance use assessment and intervention.