Realizing the vision of the IOM's landmark report, Crossing the Quality Chasm, will require new knowledge to support new policy and management. This paper lays out a research agenda that must be pursued if the health care system is to bridge the quality chasm. Based on a consensus process involving leading health care researchers and authorities, the paper highlights knowledge gaps and research directions in five areas identified by the Quality Chasm report as critical to its goals of building organizational supports for change; applying evidence to health care delivery; developing information technology; aligning payment policies with quality improvement; and preparing the workforce.