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Exertional rhabdomyolysis, a syndrome characterized by skeletal muscle degeneration and muscle enzyme leakage, has been shown to occur in normal, healthy individuals following strenuous exercise. In severe cases, this syndrome can result in renal failure and sudden death. Although anyone who performs strenuous exercise may be at risk for developing exertional rhabdomyolysis, some individuals may be more susceptible than others. A number of case reports of exertional rhabdomyolysis involve persons with sickle-cell trait, leading to the theory that these individuals might be at greater risk for developing the syndrome than those without this trait. This article discusses the etiology of exertional rhabdomyolysis, the associated risk factors for persons with sickle-cell trait, and the recommended preventive measures. Additionally, several case studies of exertional rhabdomyolysis are reviewed.