To systematically review articles reporting on depression, anxiety, and burnout among U.S. and Canadian medical students. Medline and PubMed were searched to identify peer-reviewed English-language studies published between January 1980 and May 2005 reporting on depression, anxiety, and burnout among U.S. and Canadian medical students. Searches used combinations of the Medical Subject Heading terms medical student and depression, depressive disorder major, depressive disorder, professional burnout, mental health, depersonalization, distress, anxiety, or emotional exhaustion. Reference lists of retrieved articles were inspected to identify relevant additional articles. Demographic information, instruments used, prevalence data on student distress, and statistically significant associations were abstracted. The search identified 40 articles on medical student psychological distress (i.e., depression, anxiety, burnout, and related mental health problems) that met the authors' criteria. No studies of burnout among medical students were identified. The studies suggest a high prevalence of depression and anxiety among medical students, with levels of overall psychological distress consistently higher than in the general population and age-matched peers by the later years of training. Overall, the studies suggest psychological distress may be higher among female students. Limited data were available regarding the causes of student distress and its impact on academic performance, dropout rates, and professional development. Medical school is a time of significant psychological distress for physicians-in-training. Currently available information is insufficient to draw firm conclusions on the causes and consequences of student distress. Large, prospective, multicenter studies are needed to identify personal and training-related features that influence depression, anxiety, and burnout among students and explore relationships between distress and competency.