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Since 1977, many systematic reviews have asked 2 fundamental questions: (1) Does CME improve physician performance and patient health outcomes? and (2) What are the mechanisms of action that lead to positive changes in these outcomes? The article's purpose is to synthesize the systematic review literature about CME effectiveness published since 2003.We identified 8 systematic reviews of CME effectiveness published since 2003 in which primary research studies in CME were reviewed and physicians’ performance and/or patient health outcomes were included as outcome measures.Five systematic reviews addressed the question of “Is CME Effective?” using primary studies employing randomized controlled trials (RCTs) or experimental design methods and concluded: (1) CME does improve physician performance and patient health outcomes, and (2) CME has a more reliably positive impact on physician performance than on patient health outcomes. The 8 systematic reviews support previous research showing CME activities that are more interactive, use more methods, involve multiple exposures, are longer, and are focused on outcomes that are considered important by physicians lead to more positive outcomes.Future research on CME effectiveness must take account of the wider social, political, and organizational factors that play a role in physician performance and patient health outcomes. We now have 39 systematic reviews that present an evidence-based approach to designing CME that is more likely to improve physician performance and patient health outcomes. These insights from the scientific study of CME effectiveness should be incorporated in ongoing efforts to reform systems of CME and health care delivery.