Objective: Because medical students experience a considerable amount of stress during training, academic leaders have recognized the importance of developing stress-management programs for medical students. The authors set out to identify all controlled trials of stress-management interventions and determine the efficacy of those interventions. Method: The authors searched the published English-language articles on PsycINFO and PubMed, using a combination of the following search terms: stress-management, distress, burnout, coping, medical student, wellness. Both randomized, controlled trials and controlled, non-randomized trials of stress-management programs were selected and critically appraised. Results: A total of 13 randomized, controlled trials or controlled, non-randomized trials were identified. Interventions included self-hypnosis, meditation, mindfulness-based stress-reduction, feedback on various health habits, educational discussion, changes in the length and type of curriculum, and changes in the grading system. Only one study was identified to be of very high quality, although several had described group differences at baseline, used blinding, had good follow-up, and used validated assessment tools. There was a wide heterogeneity of outcome measures used. Interventions that were supported by a reduction in stress and anxiety in medical students included mindfulness-based stress-reduction or meditation techniques, self-hypnosis, and pass/fail grading. Conclusions: Significant opportunities to advance educational research in this field exist by developing more high-quality studies with particular attention to randomization techniques and standardizing outcome measures. (Contains 1 table.)