The epidemiology and demographics of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) have evolved over the last 25 years in the United States to include more women and minority populations, especially Latinos and African Americans. In addition, there has been a shift in HIV/AIDS cases from large northeastern and western metropolitan areas to persons living in rural areas and the south. The reasons for the changes and the shift are unclear, but major barriers to primary prevention strategies are most likely sociocultural. This article reviews some of the sociocultural barriers in HIV/AIDS prevention and presents a new approach or framework for addressing these barriers. The framework highlights Stigma, Fear, and Denial as barriers in interventions for HIV/AIDS targeted at African Americans living in rural Alabama. The framework uses a culturally competent, community-based approach. It is hoped that this framework could also be used as a model for addressing HIV/AIDS in other communities, as well as addressing other health disparities where stigma, fear, and denial may play a role, such as cancer, diabetes, heart disease, immunizations, and infant mortality.