Herpes simplex virus type 2 (HSV-2) infection is almost always sexually transmitted, and causes genital ulceration. Significant progress in our understanding of HSV infection has occurred over the last decade, in part related to the development of accurate and sensitive laboratory tests to study HSV-2. The application of PCR and type-specific serology to individual cases and in population-based studies has enabled the identification of a potentially important role for HSV-2 infection as a cofactor in the sexual transmission of HIV. This is a particular issue in developing countries. This review describes the epidemiology of HSV-2 infection in the HIV era, the hypotheses regarding HSV-HIV interactions, and research priorities for the developing world.