Adolescence is a developmental stage defined in part by risk-taking. Risk-taking is critical to normal development and has important benefits including trying new activities and exploring new relationships. Risk-taking is also associated with the initiation of substance use. Because substance use often begins in adolescence, much focus has been on primary prevention with the goal of preventing initial substance use. Secondary or tertiary prevention approaches, such as counselling to eliminate substance use or offering treatment, are common approaches for adolescents with problematic substance use or a substance use disorder. While this is important, for some adolescents, treatment or cessation of use may not be desired. In these cases, Healthcare Practitioners (HCPs) can offer clear advice that incorporates harm reduction. Harm reduction, which is often applied for adults who use substances, reduces the negative impacts associated with drug use without requiring abstinence. Harm reduction is crucial to keeping adolescents safe and healthy and can offer opportunities for future engagement in treatment. The objective of this review is to describe strategies for integrating harm reduction principles in clinical settings that are developmentally appropriate. A patient-centered, harm reduction approach can validate perceived benefits of substance use, offer strategies to minimise harm, and advise reduction of use and abstinence. KEY MESSAGES: Substance use often begins in adolescence and traditional approaches are often rooted in prevention framework. Harm reduction should be incorporated for adolescents with problematic substance use or a substance use disorder. This review offers strategies for integration of harm reduction principles tailored towards adolescents.