This article argued that the radical behavioral change needed to reduce HIV transmission requires radical commitment. Reviewing 25 years of HIV prevention efforts, the authors identified successful HIV prevention interventions and ways to improve behavioral strategies to reduce HIV transmission. They stressed the need to combine behavioral, biomedical, and structural approaches to fight HIV transmission effectively. To date, behavioral changes have reduced HIV in certain countries, regions, or subpopulations because of significant behavior changes taking place among a majority of the population; a mix of communication channels providing clear, actionable risk reduction and health-seeking messages that people can choose from; and local involvement in developing, producing, and disseminating the right messages. Sustained changes in risk behavior, however, have not been found anywhere, the authors noted. They concluded that behavioral strategies must take place in combination with different approaches and at multiple levels of influence.