In the June 2 issue of the Journal of the American Medical Association (JAMA), the NHLBI's Michael Lauer, M.D., and NIH Director Francis Collins, M.D., Ph.D., eloquently describe the NIH's commitment to conducting and supporting comparative effectiveness research (CER). They note that although CER has been drawn into the health policy spotlight recently, this important research is hardly new to the NIH and the NHLBI. The goal of CER is to inform medical decision-making so the right services are provided to the right patient at the right time in the right setting. In their Commentary, Drs. Lauer and Collins showcase examples of NIH-funded CER, describe the NIH Recovery Act investment in CER, and outline five important challenges facing the NIH as we consider how to use CER to benefit health care reform.