The recent interest in diagnostic error in medicine was preceded almost fifty years ago by a focus on the problem-solving strategies of the experts of that time. This focus also extended to include the development of computer-based decision support systems to aid clinicians in diagnosis. Interest in medical errors was heightened with the publication of the Institute of Medicine report To Err is Human in 2000; however, there was still a relative neglect of the problem that diagnostic error presents. This article discusses the extent and types of diagnostic error in medicine, the challenges of studying diagnostic error, and strategies to address these errors. The role of the clinical laboratory in regard to diagnostic errors in medicine is also highlighted.