There is widespread concern about the ability of the current model of clinical research to keep pace with the growing need for testing new approaches to disease management and prevention. In response, important innovations are emerging in critical areas of research infrastructure and practice. However, success in fulfilling the promise of clinical research will also require a fundamental shift in the relationship between the clinical-research enterprise and all segments of society. In this article, we outline proposals to help create the necessary recognition and engage participation by patients, clinicians, health-care delivery systems, and the research community to establish the long-lasting growth needed for achieving the full potential of clinical research.