The partial efficacy of the recent HIV-1 vaccine trial in Thailand has rejuvenated the HIV vaccine field. There are now clear opportunities to dissect the potential correlates of protection against HIV-1. Comparisons of three major HIV-1 vaccine strategies used in human efficacy trials to date highlight a possible role for antibody-dependent cellular cytotoxicty (ADCC), rather than cytotoxic T lymphocyte or neutralizing antibody responses, in protective immunity. This review explores the HIV vaccine efficacy trials performed to date and the potential role for ADCC antibodies in assisting protective immunity.