Recent innovative research has identified key factors that put vulnerable South African women at risk of HIV/AIDS and gender-based violence, including high-risk patterns of alcohol abuse and sexual partnering, gender norms that place men in control in sexual relationships, low educational levels and limited access to employment, poor health care, inadequate housing, and sex work. These studies identified vulnerable populations of South African women as female drug users in Pretoria and Cape Town, female sex workers in Cape Town, Durban and Pretoria, young rural women in Eastern Cape and drug-using girls out of school in Cape Town. The research suggests that targeted HIV-prevention interventions can effect improvement for this vulnerable population when programs remain sensitive to gender and cultural differences and expectations and address the social and economic inequalities that make women vulnerable.