Adolescence is a unique period of physical and psychosocial changes as youth transition, over many years, to adulthood. The psychosocial changes that accompany adolescence include emotional separation from parents, greater influence of peer groups, an interest in self-identification and autonomy, and increased risk-taking behaviors. Substance use is a common form of risk-taking behavior in the adolescent developmental stage. Alcohol, nicotine, and cannabis are the most common types of substances used in the United States. In the adolescent transplant population, rates of substance use appear to be at, or slightly below, their peer counterparts. Substance use can lead to deleterious health outcomes for adolescent transplant patients as a result of impaired decision-making, reduction in medication and clinic visit compliance, increases in mental health disorders, and risk for developing dependence and a substance use disorder. Given the close relationship that many pediatric transplant providers have with their patients and families, transplant care teams are in an excellent position to help their patients by addressing adolescent substance use. This narrative review describes how providers can use proactive standardized approaches to identify and intervene with substance use behavior.