Comparative Effectiveness Research (CER) has recently emerged as a major theme in health care reform. Unfortunately, there is a widespread lack of understanding about what it will do and fear that it will do more harm than good. These concerns include threats to individual physician's autonomy and professionalism, as well as fears that care will be rationed based on such findings. In this paper, we argue that the main components of the current healthcare reform (HCR) bills, which include expanding insurance while increasing efficiencies through cost containment, should embrace CER. This type of research will provide a "safeguard" against "blind" cost-containment, so that the new financial incentives being introduced can be actualized effectively and safely. Evidence for this is provided from examples from the authors' prior and current research as well as from the literature. We also argue that the requirement for data from CER will create long-term disincentives for "me-too" drugs and devices and, therefore, become a catalyst for effective innovation.