Background: Acne is a very common problem with significant physical and psychological morbidity. The evidence basis for its treatment had not been systematically reviewed. Therefore, we performed an evidence review to provide researchers a basis for further studies, and to provide clinicians the background needed to interpret current and future clinical studies. Objective: We summarize the methodologic state of the acne literature in patients with acne who do not have complicating co-morbidities. Methods: This was an expert-advised literature synthesis. We used a structured literature search for English-language controlled trials in Cochrane CENTRAL, MEDLINE, OLDMEDLINE, HSTAT, CINAHL, and PsychInfo. Results underwent a structured data abstraction process, with review by at least 2 reviewers. Results: Out of 1588 unique articles, 250 articles (274 controlled trials) over the past 50 years were reviewed: 57 (21%) trials had at least one major weakness and no strengths; 125 (47%) trials had at least one major strength and at least one major weakness; 48 (18%) trials had at least one major strength, and no major weaknesses. The remaining 16 (6%) were of intermediate quality or did not provide enough information to make a determination. One fourth of studies did not report patient age; one fourth did not report on patient gender. Only 8% mentioned patient race; only 2% mentioned skin type; 0.4% mentioned diet; none scored sexual maturity or insurance status. There were 1237 outcomes. There were more than 25 methods of assessing acne severity and more than 19 methods for counting lesions. There were only two trials that formally assessed psychological outcomes. More than 140 treatments were tested in 251 comparisons. Conclusion: Ranging over 50 years of research, the acne literature evidences great heterogeneity at all levels: patient characteristics, acne severity, outcome assessments, treatments, and comparisons. A list of methodologic recommendations is provided. (J Am Acad Dermatol 2002;47:231-40.)