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The effects of sleep loss and fatigue in the context of medical training is a topic that has generated considerable interest, as well as controversy, over the past two decades. The sleep deprived state in medical trainees potentially impacts on a variety of domains relevant to medical care, including performance on neurobehavioral and work-related tasks, mood and affect, learning, risk for and commission of medical errors, and the health and well-being of medical students and residents. The following review provides a summary of research conducted on this topic in the past decade, including the relation of sleep loss and fatigue to medical errors and the quality of patient care. Those few studies that have analyzed the use of operational alertness management strategies, countermeasures, and educational interventions to address and mitigate the effects of sleep loss and fatigue are also reviewed. There is clearly a need for additional research to further explore the complex interaction between sleep and fatigue and medical care, and to support the development and implementation of regulatory policies based on sound science.