The United States is making a sizable investment in CER in the hope that the results will influence the decisions of clinicians and patients and optimize the quality and costs of care. Attention to the root causes of ineffective CER translation seems critical. The policy options that emerged from our case studies of five prominent CER projects appear to us to have the greatest potential to address key factors that may lead to failure of CER to influence clinical practice. These results underscore the complexity of introducing CER evidence. Despite that complexity, it appears that a relatively finite number of policy changes, carefully selected, could enhance the impact of CER in the future. Taken together, these policy options suggest a number of different paths forward, and exploring multiple approaches may be appropriate given the large number of factors that impede CER translation. As the ARRA-financed CER portfolio begins to produce new evidence, a number of opportunities will exist to experiment with these approaches.