The opportunities for researchers to improve health and health care by contributing to the formulation and implementation of policy are almost unlimited. Indeed, the availability of these opportunities is a tribute to a generation of health services researchers questioning existing policies or studying essential “Why?” and “What if?” questions using rigorous analysis. Moreover, the steady albeit uneven transition of health care delivery from a paper-based cottage industry toward an enterprise that provides transparent information to clinicians, patients, policy makers and the public, and potentially vast amounts of data to policy researchers, combined with the expectations of an increasingly information-savvy public, have increased the focus on health care quality, access, and costs. Our health care system, like those in other countries, confronts continued pressures from increasing costs; inconsistent quality; avoidable patient harms; pervasive disparities in health and health care associated with individual characteristics such as race, ethnicity, income, education and geography; and poor population health outcomes. The persistence of many of these challenges reflects, in part, a failure of science alone to improve heath. Strategies to address many of these challenges exist in the laboratory, but the contribution of this science to the health of the public is limited by a research enterprise that values discovery of new knowledge far more than its successful application. The Robert Wood Johnson Foundation (RWJF) Clinical Scholars Program, now approaching its 40th birthday, was designed to create “change agents” for the U.S. health care system by training physicians interested in creating and applying innovative research or other approaches to address important societal health challenges. Prior scholars have received advanced training in fields from anthropology and history to business administration. Alumni of the program have served in major leadership roles in both public (federal and state governments, health departments) and private (health systems, business, nonprofit organizations, medical professional organizations) sector organizations for many years. This unprecedented long-term investment in human capital has yielded leaders who have made a tangible difference in health policy. Those leaders have forged new paths that blend clinical training and expertise with science-informed policy development and implementation, whether in academia, government, or the private or nonprofit sectors. This commentary, by authors now directly engaged in policy, describes the ways that research influences policy and offers reflections on the culture and imperatives of a policy environment.