The CAPRISA 004 clinical trial of 1% tenofovir gel, conducted by South African investigators and jointly supported by USAID and the Government of South Africa, was the first demonstration that a vaginal microbicide could significantly reduce the risk of HIV infection. This proof of concept, announced in July 2010, focused attention on the need to confirm the safety and effectiveness of this product, obtain regulatory approval from the relevant national authorities, and prepare for introduction of this new HIV prevention technology designed to help meet the needs of women in developing countries. Simultaneously, other promising microbicide leads are moving forward in the product development pipeline as well. Although research and development (R&D) for improved and alternative microbicide products will continue to be of interest, a new and broader range of activities is now needed to move the USAID program forward toward microbicide introduction.