This paper has five objectives: (a) to review the scientific background of, and major findings reported in, Medical Problem Solving, now widely recognized as a classic in the field; (b) to compare these results with some of the findings in a recent best-selling collection of case studies; (c) to summarize criticisms of the hypothesis-testing model and to show how these led to greater emphasis on the role of clinical experience and prior knowledge in diagnostic reasoning; (d) to review some common errors in diagnostic reasoning; (e) to examine strategies to reduce the rate of diagnostic errors, including evidence-based medicine and systematic reviews to augment personal knowledge, guidelines and clinical algorithms, computer-based diagnostic decision support systems and second opinions to facilitate deliberation, and better feedback.