After the disappointing news reported at the 2008 (15th) Conference on Retroviruses and Opportunistic Infections regarding HIV vaccines, microbicides, and herpes virus suppression trials, the 16th conference this year brought welcome advances in the HIV prevention field. In particular, substantial progress is being made in approaches to preexposure prophylaxis in preclinical and clinical trials, and an efficacy trial of a vaginal microbicide appeared to provide women in Africa and the United States with modest protection against HIV acquisition. This review covers presentations on the epidemiology of HIV infection in specific global populations, strategies to improve the uptake of HIV testing, lessons from previous negative prevention trials, and progress in the development of new biomedical interventions.