This chapter focuses on the enormity of preventable medical errors that cause injury or death and one root cause associated with those errors called “human factors”. Human factors have been identified as a root cause of medical errors, particularly diagnostic errors. The chapter talks about latent failures, mental models, misdiagnosis, and sentinel event. The science of psychology and physiology tells us that the human mind works very rapidly, which raises the risk of making a judgment error. Human factors reengineering is discussed as a much-needed mechanism to address fixation errors and decrease diagnostic errors. Misdiagnosis is much too common in health care. A diagnostic fixation error is a phenomenon of clinging to a single presumed diagnosis despite mounting evidence that one is on the wrong track. The application of human factors engineering can and should include data from patients and their families so as to capture the most optimal solutions.