People with pain have no shortage of treatment options offered to them. The labyrinth of options poses difficult choices for patients and clinicians. Key to making those choices is evidence of treatment effectiveness provided by clinical trials and systematic reviews. Recent increases in the number of clinical trials and systematic reviews, of both high and low quality, makes it vital that users of this evidence-clinicians, researchers, patients, and policy makers-have the skills and knowledge to critically interpret these studies. In this review, some contemporary issues regarding evidence of effectiveness derived from clinical trials and systematic reviews-issues that the authors believe to be critical to understanding the field are discussed. It focuses on evidence of treatment effectiveness in pain, although many of these issues are relevant to and transferable across the spectrum of evidence-based practice.