Drug, alcohol, and tobacco use is highly prevalent among high school students in United States, and adolescents, even those without a substance use disorder, are at high risk of morbidity and mortality related to use of these substances. The primary care setting provides access to adolescents, and the health maintenance visit provides a private, confidential setting in which patients expect to discuss health-related behaviors and receive advice. This article reviews guidelines for identifying and managing adolescent substance use in the primary care setting, including screening, brief intervention, and referral to treatment.