Incarceration and HIV/AIDS disproportionately affect African American men compared to the U.S. population as a whole. Disparities in relation to crime and HIV/AIDS for Black men suggest that these phenomena have elements in common, particularly given the mediating role of illicit drug use or drug activities in both cases. A socioecological exploration of how and why these twin epidemics intersect (and the role of drug-related activities as mediating variables) is needed illicit drug use or to address the impact of these epidemics on the health and well-being of communities of color. This article critically reviews relevant articles, research reports, and official statistics, as well as conceptual frames of reference for information on the socioecological synergies between crime, drugs, and HIV/AIDS. The article recommends five calls for action for policies to mitigate the cumulative negative effects of these epidemics and for interventions to enhance the life chances of at-risk Black men.