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Numerous historical accounts suggest the presence of mental illness in US Presidents, but no systematic review has been undertaken for all holders of this office. We reviewed biographical sources regarding mental illness in 37 US Presidents from 1776 to 1974. Material was extracted by one of the authors and given to experienced psychiatrists for independent review of the correspondence of behaviors, symptoms, and medical information in source material to DSM-IV criteria for Axis I disorders. Levels of confidence were given for each diagnosis. Eighteen (49%) Presidents met criteria suggesting psychiatric disorder: depression (24%), anxiety (8%), bipolar disorder (8%), and alcohol abuse/dependence (8%) were the most common. In 10 instances (27%), a disorder was evident during presidential office, which in most cases probably impaired job performance. Mental illness in heads of state is a topic deserving further attention. Methodological limitations of using biography to determine psychopathology are discussed.