PIP: While safer sex campaigns have reduced the incidence of HIV in many parts of the world, behavioral interventions alone will not be able to keep the virus from spreading. Safe and effective vaccines are urgently needed to help prevent infections, as well as to stop infection from developing into disease. The head of the World Health Organization Global Program on AIDS's (GPA) vaccine development unit and his colleague report on the state of vaccine development and on GPA's vaccine strategy. The ideal vaccine would protect all people against the transmission of all HIV subtypes through all routes, would require as few doses as possible and not require refrigeration, and be affordable in developing countries where 80% of all HIV infections occur. Fifteen candidate vaccines have entered phase I human trials to assess their safety and immunogenicity, of which two made it to phase II trials. None, however, has made it to phase III. General agreement does not even exist on the criteria for admitting a candidate vaccine to large-scale, phase III efficacy trials. Nonetheless, vaccines evaluated in seronegative volunteers have been found to be largely safe and well-tolerated in doses capable of inducing HIV-specific immune responses, but it is unclear whether they will be able to protect people from infection with HIV or prevent/delay the onset of AIDS in those already infected. Many questions remain to be answered.