Comparative effectiveness research (CER) stands out as the intriguing wild card of health care reform. CER compares competing treatments against each other to determine which interventions work best, supplying critical information for medical decision making and health policy. If CER works as planned, it may be one of the few reform measures in the final health care legislation that could flatten the cost curve while also improving quality. Unfortunately, health care reform has so far failed to bet smart and play the CER wild card effectively. While the Patient Protection and Affordable Care Act invests in CER at record levels and creates an entirely new regulatory framework for oversight of the research, the new law does very little to advance the difficult work of translating CER into actual medical practice. First, CER is costly to conduct and its data often raise more questions than answers. Second, the government's CER agenda seems vague and ill-defined, not consistently focusing on generating research that will help clinicians resolve immediate treatment questions. Third, and most important, physicians likely will remain indifferent to and "tune out" CER. Health law and policy are not setting the right incentives for physicians to adapt their practice patterns to CER and, in some respects, exacerbate the physician-engagement difficulties. The reasons for physician indifference to CER include: lack of financial incentives, suspicions of industry bias in the public/private oversight of the research, threats to clinical autonomy, a commitment to individualized medicine (encouraged by health law, professional ethics, and medical norms) that remains in tension with CER, concerns that CER is a vehicle for crude cost-cutting, and malpractice liability fears. To be truly effective, the new national CER program requires targeted reforms designed to engage physicians more directly with the research. This Articles principal suggestions include greater linkage of CER with reimbursement and liability incentives, enhanced use of academic detailing, and more support for comparative implementation studies that evaluate different strategies for fostering physician uptake of CER.