Experienced diagnosticians rely on heuristics—rules of thumb—to recognize clinical patterns and establish diagnoses efficiently. However, this process can lead to diagnostic error, as numerous cognitive biases can adversely affect the diagnostic reasoning process. This two-part series reviews the psychological origins of cognitive biases, examines the theoretical basis behind "debiasing" approaches (strategies for averting specific cognitive biases), and proposes a framework for preventing diagnostic errors through educational and systems-based approaches. Two of the most common cognitive biases, premature closure (diagnosing a patient on the basis of preliminary or incomplete information) and anchoring (failing to reconsider a provisional diagnosis in the face of conflicting information) are vividly illustrated in an AHRQ WebM&M commentary. Dr. Pat Croskerry, the lead author of these articles, was interviewed by AHRQ WebM&M in 2010.