Over the past century, medical advancements have resulted in tremendous health gains for Americans. Although the federal government has played a prominent role in ensuring that new treatments are safe and effective, questions about which medical treatments work best under which circumstances have largely remained unanswered. Thus, the federal government's recent major investments in comparative-effectiveness research have potential to play a significant role in helping both patients and health care providers navigate the vast array of available treatment options, as well as in improving the quality, efficiency, and delivery of health care system-wide. Yet, the controversial nature of the government's foray into comparative-effectiveness research also suggests that the path toward realizing these goals may be treacherous. This Article describes the rationales for federal support of comparative-effectiveness research and potential models for that involvement, analyzes the federal government's recent investments in the research, and concludes with predictions about the probable outcomes of these investments. While increased federal support for comparative-effectiveness research is unlikely to achieve all of the benefits anticipated by its supporters, it is a crucial step toward ensuring that Americans are able to take full advantage of the benefits of medical innovation.

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