The World Health Organization estimates that 50% of the 30 million HIV infections worldwide occurred in young people between the ages of 15 and 24 years. In the United States, national statistics estimate that almost 40% of new HIV cases occur in youth ages 13-29 (Centers for Disease Control and Prevention, 2011). Therefore, a focus on preventing HIV/AIDS among adolescents and young adults is warranted. There has been success in developing efficacious interventions for adolescents that reduce HIV sexual risk behaviors; however, the HIV incidence rates among adolescents remain alarming. This article identifies four areas of intervention development that remain underdeveloped and may guide the next generation of HIV prevention interventions. Family-based interventions, addressing health disparities and understanding the social determinants of health for adolescents, expanding the theoretical models that are relied on in developing interventions, and utilization of new technologies each have promise for successfully assisting adolescents to reduce their risk behaviors and enhance protective factors.