Control of human immunodeficiency virus type-1 (HIV-1) infection is the foremost public health challenge at the turn of the millennium. Two decades, 22 million fatalities, and 40 million living victims after its discovery, HIV-1 continues its inexorable spread. Over the past few years, scientists have made tremendous progress in understanding the immunopathogenesis of HIV-1 infection and identifying potential targets for intervention with vaccines. Future progress will require a coordinated and proactive response to foster understanding of the benefits of vaccines and to encourage a receptive atmosphere for community vaccine testing and implementation.