Prevention efforts for HIV-1 have traditionally focused on those at risk for acquiring the virus. Recently, there has been growing interest in directing prevention efforts towards HIV-1-seropositive individuals, who are seeking care in increasing numbers as a result of improving access to antiretroviral therapy in resource-limited countries. Biomedical interventions aimed at reducing the spread of HIV-1 by targeting those at risk for transmitting the virus will be guided in part by an understanding of the bidirectional interactions between HIV-1 and other sexually transmitted diseases (STDs). Among those who are infected with HIV-1, STDs are common, and immunosuppression may further increase STD risk. In turn, the presence of an STD increases the concentration of HIV-1 in genital mucosal secretions. Both antiretroviral therapy and treatment of STDs can lower genital HIV-1 concentrations, suggesting that these approaches may reduce infectivity. Thus, the growing availability of HIV-1 and STD treatment in the countries most affected by the HIV-1 epidemic provides a unique and important opportunity to develop prevention strategies that target HIV-1/STD interactions at multiple levels. Further work is urgently needed to develop, test and implement comprehensive strategies for prevention in positives.