The HIV epidemic continues to disproportionately affect ethnic minority youth. These disconcerting health disparities indicate that although existing HIV preventive strategies for ethnic minority youth have been efficacious, they have not significantly reduced the impact of the epidemic in this population. Macro-level interventions, such as structural or policy interventions, have the potential to impact the HIV epidemic at a population level, and thus reduce the HIV health disparities that exist among ethnic minority youth and other segments of the U.S. population. This article calls for a paradigm shift to develop, evaluate, and disseminate interventions that target upstream/macro-level factors or that, at a minimum, integrate both a macro and individual level perspective. The article also discusses the challenges in developing and evaluating such interventions. Psychologists and other behavioral scientists can play a critical role in reducing the impact of HIV on ethnic minority youth by integrating macro-level approaches to future HIV prevention strategies.