In the fall of 2007, the HIV-1 research field received news that their front-runner vaccine was not protective. In response to this disappointment, scientists are now reviewing the intricacies of the immune response toward HIV-1 to develop new and better strategies for vaccine development. Decades ago, researchers recognized the impressive amino acid and carbohydrate diversity of HIV-1, and the associated obstacles to vaccine development. At first glance, the diversity and other unique features of HIV-1 may seem insurmountable, but attention to vaccine successes in other fields serves to renew optimism. The newly-licensed rotavirus and papillomavirus cocktail vaccines remind scientists that diverse pathogens can be conquered and that the chronic nature of a virus infection need not thwart successful vaccine design. Here we describe current efforts to gain insights from other vaccine fields and to adopt a cocktail vaccine approach for the prevention of HIV-1 infections in humans.