The act of diagnosis begins with human cognition, and diagnostic excellence requires sound thinking. The skill set to acquire accurate and complete information, distill important clinical signals from the noise of irrelevant or distracting elements, interpret data, and synthesize the parts into a cohesive whole is complex and deserves study.Having medical knowledge and knowing how to perform each step of diagnosis are not sufficient to avoid errors if the reasoning process is flawed or lacking selfawareness or insight into its limitations. Challenges abound to potentially interfere with human rationality, 1 including the constant noise that runs interference against human judgment. 2 According to one model, 3 the diagnostic process entails more than 50 independent factors that cluster into 6 domains: the clinician's individual characteristics (sex, age, experience, and others); features of individual cognitive processes; factors that could adversely affect individual homeostasis; ergonomic and other characteristics of the workplace; features of the particular disease, its manifestness, presentation, and context; and characteristics of the patient and their presentation of the disease.While each of these factors may exert its own main effect, the diagnostic process may be complicated further when 2 factors interact in a first-order interaction (eg, physician sex with the patient's cultural background) or through a second-order interaction in which 3 factors may be involved. All of these factors and their interactions are capable of generating noise that may interfere with the detection of the diagnostic signal. Wellcalibrated, rational decision-making is difficult to achieve, reflected in a significant diagnostic failure rate (defined as "the failure to (a) establish an accurate and timely explanation of the patient's health problem(s) or (b) communicate that explanation to the patient" 4 ). Such errors account for an estimated 6% to 17% of hospital adverse events. 4 Even assuming a diagnostic accuracy rate of 85%, most physicians and patients would likely prefer an even greater level of accuracy and certainty.Awareness of cognitive factors that may contribute to errors of judgment and decision-making has been known since at least the time of the ancient Greeks. In the 1970s, experimental evidence from Kahneman and Tversky illustrated the nature of cognitive bias and also provided proof of its influence on judgment and decisionmaking, culminating, in 2002, in the second of 2 Nobel prizes that have been awarded for decision-making (the earlier one having gone to another psychologist, Herbert Simon in 1978). Not surprisingly, vulnerability to cognitive bias is considered the major potential threat against sound clinical decision-making, the medical