Sexual behavior can threaten the physical and social well-being of young people in the United States in a variety of ways, as it can put them at risk for infection with the human immunodeficiency virus (HIV), other sexuallytransmitted diseases (STDs) and unintended pregnancy. This review describes the current extent of HIV infection in American adolescents, identifies and characterizes particular high-risk groups and risk-bearing and protective behaviors, and identifies barriers to adopting preventive behaviors and using health care services. Our main focus is to present findings from intervention research; we summarize the effects of strategies that operate at the individual level (i.e. biomedical or behavioral, in and outside of the clinic) and environmental level (i.e. family, school and community behavioral) to influence behavioral change and the prevention of HIV infection. Overall, even though abstinence eliminates the risk altogether and the use of condoms can effectively reduce the risk of sexual transmission of HIV, adolescents do not optimally employ these practices. Various approaches to counseling by providers and other behavioral interventions aimed at reducing high-risk sexual behavior have been effective, but have met with limited and short-lived success. Among the areas receiving inadequate attention to date have been the link between biomedical and communitybased behavior change interventions and the correspondence of biologic and behavioral outcomes. These areas are explored and directions for future research are suggested.