To underscore the public health risk involved, as well as the extent to which HIV infection rates disproportionately affect racial/ethnic populations in prison settings, the authors briefly review a current approach that is being implemented in four selected sites located in the southeastern region of the United States. Moreover, the authors present these observations in terms of HIV infection and how health professionals may be able to curb the spread of this and other infectious pathogens among primarily incarcerated African American and Latino male inmates. Based on a peer education model, the authors outline several practice implications for dealing with this population, which include (a) making provisions for case management, (b) building capacity and increasing the participatory role of community agencies, (c) focusing on the significance of ethnicity and cultural competency in prison culture, (d) implementing youth-specific models, and (e)applying a holistic approach.