There is growing consensus that the U.S. health care system is not producing value relative to the resources invested. Unwarranted variation exists in quality and outcomes of care and underutilization of both evidence-based medicine and evidence-management practices. To address these issues, this article calls for a broad-based social science approach focused on obtaining a greater understanding of change at the individual, group, organizational, and environmental levels as they influence each other. Specific examples and questions for research are suggested with regard to the redesign of care systems, enhancing learning and transferring knowledge, and creating effective financial incentives. The specific measurement, analysis, and study design issues involved in under-taking such a research agenda are discussed.