This article articulates a contextualized understanding of gender and ethnicity as interacting social determinants of HIV risk and acquisition, with special focus on African Americans and Hispanics/Latinos--2 ethnic groups currently at most risk for HIV/AIDS acquisition in the United States. First, sex and gender are defined. Second, a conceptual model of gender, ethnicity, and HIV risk and resilience is presented. Third, a historical backdrop of gender and ethnic disparities is provided, with attention to key moments in history when notions of the intersections between gender, ethnicity, and HIV have taken important shifts. Finally, new frontiers in psychology are presented, with recommendations as to how psychology as a discipline can better incorporate considerations of gender and ethnicity as not only HIV risk factors but also as potential avenues of resilience in ethnic families and communities. Throughout the article, we promulgate the notion of a syndemic intersectional approach, which provides a critical framework for understanding and building the conditions that create and sustain overall community health by locating gendered lived experiences and expectations within the layered conceptual model ranging from the biological self to broader societal structures that define and constrain personal decisions, behaviors, actions, resources, and consequences. For ethnic individuals and populations, health disparities, stress and depression, substance abuse, and violence and trauma are of considerable concern, especially with regard to HIV risk, infection, and treatment. The conceptual model poses new frontiers for psychology in HIV policy, research, interventions, and training.