The evidence-based practice movement rests on the premise that the scientific evidence regarding treatment should be used judiciously to inform treatment decisions. This article focuses on the most fundamental question regarding evidence-based practice: What is evidence? To address this question, the authors first review several of the definitions, criteria, and strategies that have been used to define scientific evidence. Second, a number of critical issues that have been raised regarding the nature of treatment evidence are discussed. Finally, suggestions for further consideration in the process of synthesizing evidence for clinicians are offered.