The HIV epidemic among adolescents in the United States is inherently tied to individual, psychosocial, and cultural phenomena. Expanding intervention development and implementation to incorporate a broader spectrum of determinants of adolescents' sexual risk for sexually transmitted infections (STIs)/HIV acquisition may provide an opportunity to prevent disease transmission more effectively. To address the STI/HIV prevention needs of adolescents, we highlight research assessing adolescents' sexual risk behavior and place the findings in the context of the diverse array of psychosocial factors influencing adolescents. This synthesis provides an opportunity to examine why adolescents engage in risky sexual behavior and to review the effectiveness of theory-based prevention programs. Subsequently, we offer recommendations for improving future programs aimed at reducing the incidence of STI/HIV infection among adolescents.