The majority of the world's HIV infections occur in communities ravished by poverty. Although HIV/AIDS and poverty are inextricably linked, there are few studies of how poverty-related stressors contribute to HIV risk behavior practices. In this study, surveys were conducted in three South African communities that varied by race and socio-economic conditions: people living in an impoverished African township (N = 499); an economically impoverished but well infrastructured racially integrating township (N = 995); and urban non-impoverished neighborhoods (N = 678). Results showed that HIV/AIDS risks were closely related to experiences of poor education, unemployment, discrimination, violence, and crime. Although poverty-related stressors were associated with a history of alcohol and drug use, substance use did not moderate the association between poverty-related stressors and HIV risk behaviors. The findings suggest that HIV prevention strategies should not treat AIDS as a singled out social problem independent of other social ills.