Comparative effectiveness research aims to inform health-care decisions by patients, clinicians, and policy makers. However, questions related to what information is relevant, and how to view the relative attributes of alternative interventions have political, social, and medical considerations. In particular, questions about whether cost is a relevant factor, and whether cost-effectiveness is a desirable or necessary component of such research, have become increasingly controversial as the area has gained prominence. Debate has emerged about whether comparative effectiveness research promotes rationing of cancer care. At the heart of this debate are questions related to the role and limits of patient autonomy, physician discretion in health-care decision making, and the nature of scientific knowledge as an objective good. In this article, we examine the role of comparative effectiveness research in the USA, UK, Canada, and other health-care systems, and the relation between research and policy. As we show, all health systems struggle to balance access to cancer care and control of costs; comparative effectiveness data can clarify choices, but does not itself determine policy or promote rationing of care.