The worlds of prevention research and practice are largely disconnected. The growing body of scientific knowledge regarding effects of prevention programs is not often disseminated and translated in a manner that leads to wide scale changes in practice. The Centers for Disease Control and Prevention, in collaboration with a team of academic researchers, has developed the Interactive Systems Framework for Dissemination and Implementation to help us understand the roles and interactions of those associated with developing knowledge, those associated with using the knowledge in practice settings, and those acting in the roles of bridge, support, and broker between the research and practice communities. This special issue on the Framework presents a variety of theoretical, practical and empirical issues related to this framework and its subsystems. This compilation of articles discuss the capacity of the Framework's subsystems, provide examples of the generally under-developed prevention support system, describe the additional challenges involved in disseminating a change in culture, discuss the delicate balance and interaction of fidelity and adaptation, present a meta-analysis of the relationships between program implementation and program outcomes, and include examples of how the Framework has been used to guide action. The present commentary on this special issue provides a critical examination of the contributions, implications, and challenges raised by each of these articles. It also includes a discussion of how the Framework relates to the basic values and practice of community psychology and concludes with some suggested future directions and challenges for the continued development and use of the Framework.