Risky behaviors such as substance use, unsafe sexual interactions, aggression, and antisocial behavior are often elevated during adolescence and can serve as powerful influences on both youth adjustment and long-term mental and physical health outcomes. The various stages of adolescence, from early adolescence to emerging adulthood, present novel opportunities and challenges, often introducing new risk-taking opportunities. Underlying adolescents’ risk behaviors during this developmental period are extensive cognitive, biological, and social factors including brain development, new and renegotiated relationships, and contextual considerations such as socioeconomic status, community resources, and identity-related stress. Current interventions target risk behaviors at a variety of levels, focusing on individuals, families, schools, and communities, with many of these efforts demonstrating success with different populations. Future research and prevention efforts will continue to benefit from targeting multiple co-occurring behaviors, considering social influences of underserved groups facing disparities in risk-taking behaviors, culturally adapting interventions, and including other caregivers such as fathers.