The National Oncologic PET Registry (NOPR) was one of the first attempts of the Centers for Medicare & Medicaid Services (CMS) at coverage with evidence development. Under this coverage policy, the agency will provide payment for a technology only if patients and providers agree to enroll in a prospective study or registry. The NOPR was designed to determine if the results of positron emission tomography scans influence physicians' intended plans of patient management while imposing minimal restrictions on the use of such scans in the clinical setting. The experience of policymakers, methodologists, physicians, and patients with the NOPR provides some useful insights into the utility and challenges of implementing, financing, and creating a robust methodology for coverage with evidence development in the future. Moving to a system of evidence-based medical technology diffusion will require all health care decision makers to become involved in evidence generation and reach an agreement about the type of evidence required to make informed medical decisions.