Randomized controlled clinical trials remain the best method for minimizing bias when evaluating dermatological treatments. Many dermatologic clinical trials have suffered from small sample sizes, selective reporting of outcomes, publication bias, poor reporting, and heterogeneous outcomes that have hampered comparability-deficiencies that can be overcome by adopting good trial planning and reporting practice encouraged by this journal. Although a profusion of explanatory placebo-controlled studies have contributed little to decision making in the clinical setting, some comparative effectiveness trials such as the use of topical corticosteroids for pemphigoid may have played a pivotal role in improving the well-being of dermatological patients. Systematic reviews (SRs) of clinical trials strive to organize the entire body of evidence while minimizing bias so that policy makers and guideline developers can base their recommendations on the appropriate strength and level of evidence. In dermatology, SRs, such as those undertaken by the Cochrane Collaboration, have produced clear clinical messages despite conflicting individual studies, and also play a key role in identifying research gaps. Future challenges include optimizing the use of research resources, adopting methodological developments in health technology assessment, and prospective registration and complete reporting of all study results.