2006 is the 25th anniversary of the AIDS epidemic and the 10th anniversary of the potent antiretroviral therapy era. During this period, the annual Conference on Retroviruses and Opportunistic Infections (CROI) has grown to represent one of the most important meetings of the year with respect to providing a forum for investigators to present the latest information on developments in the antiretroviral therapeutic arena. This year's conference maintained this tradition and was most notable for the presentations on new antiretroviral agents, therapeutic strategies including major results of treatment interruption studies, viral resistance, and encouraging results of antiretroviral rollout programs in the developing world which have brought us to the threshold of a new era in treatment and clinical investigation.