South Asia's HIV epidemic is highly heterogeneous. As a result, informed, prioritized, and effective responses necessitate an understanding of the epidemic diversity between and within countries. Further spread of HIV in South Asia is preventable. The future size of South Asia's epidemic will depend on an effective two-pronged approach: firstly, on the scope and effectiveness of HIV prevention programs for sex workers and their clients, injecting drug users and their sexual partners, and men having sex with men and their other sexual partners; and secondly, on the effectiveness of efforts to address the underlying socio-economic determinants of the epidemic, and to reduce stigma and discrimination towards people engaging in high risk behaviors, often marginalized in society, as well as people living with HIV and AIDS. This review was undertaken to provide a basis for rigorous, evidence-informed HIV policy and programming in South Asia.