Despite major advances in HIV treatment and progress in distribution of antiretroviral therapy in the developing world, staggering rates of new HIV infections persist. Innovative approaches to prevention of transmission are needed. Recent data have confirmed previous observational studies that demonstrated a substantial reduction in acquisition risk with male circumcision and microbicide technology experienced a setback with the early termination of a large-scale vaginal microbicide trial of cellulose sulfate. Limited data from one trial of pre-exposure prophylaxis was not able to validate nor refute efficacy. This article summarizes a presentation on biomedical prevention of HIV infection made by Raphael J. Landovitz, MD, at an International AIDS Society-USA Continuing Medical Education course in Los Angeles in March 2007.