We propose a set of common factors in evidence-based interventions (EBI) for HIV prevention, which cut across theoretical models of behavior change. Three existing literatures support this agenda: (1) Common factors in psychotherapy; (2) core elements from the Centers for Disease Control and Prevention EBIs; and (3) component analyses of EBI. To stimulate discussion among prevention researchers, we propose a set of common factors at the highest level of abstraction that describe what all effective programs do: (1) establish a framework to understand behavior change; (2) convey issue-specific and population-specific information necessary for healthy actions; (3) build cognitive, affective, and behavioral self-management skills; (4) address environmental barriers to implementing health behaviors; and (5) provide tools to develop ongoing social and community support for healthy actions. A focus on common factors will enhance research on new HIV prevention interventions, encourage collaboration among researchers, provide guidelines for adapting EBI, and simplify and speed the adoption of EBI for providers.