The great majority of medical diagnoses are made using automatic, efficient cognitive processes, and these diagnoses are correct most of the time. This analytic review concerns the exceptions: the times when these cognitive processes fail and the final diagnosis is missed or wrong. We argue that physicians in general underappreciate the likelihood that their diagnoses are wrong and that this tendency to overconfidence is related to both intrinsic and systemically reinforced factors. We present a comprehensive review of the available literature and current thinking related to these issues. The review covers the incidence and impact of diagnostic error, data on physician overconfidence as a contributing cause of errors, strategies to improve the accuracy of diagnostic decision making, and recommendations for future research.