A systematic framework for prevention science clinical research is described that explicitly links the identification of prevention needs to the implementation of research results in public health programs. The framework integrates five elements: advocacy and policy, community participation, prevention research, acceptability research, and operations and program development. These five elements are often viewed as disparate agendas, but an effective prevention science research enterprise requires that they be coordinated and integrated through all research stages--from the conceptual, to the experimental, and ultimately to the applied. Examples are provided of how this integration can be achieved from our experience in reproductive health and HIV prevention.