The highlight of the 2008 Conference on Retroviruses and Opportunistic Infections was a sober assessment of the HIV vaccine field by one of its pioneers. Desrosiers delivered a plenary session in which he called for refocusing our HIV vaccine effort. He suggested that none of the current vaccine candidates in human clinical trials stands a chance against HIV. Thus, we need to redirect our efforts to basic vaccine research. This call for a sea change in how we carry out HIV vaccine research has already had an impact, prompting a recent HIV vaccine summit in Bethesda, MD. This will likely herald a new era in HIV vaccine research, resulting in a redoubling of effort to uncover innovative new ways of making an HIV vaccine.