Acute exertional rhabdomyolysis is caused by a skeletal muscle injury that results in the release of myoglobin and other cellular contents into the circulatory system. Recent reports suggest that acute exertional rhabdomyolysis is more common and more serious than previously realized. Mild to moderate acute exertional rhabdomyolysis can result in hyperkalemia, hypernatremia, lactic acidosis and hyperphosphatemia. Disseminated intravascular coagulation, renal failure and compartmental syndrome may also occur. The physician should maintain a high index of suspicion for acute exertional rhabdomyolysis in patients who present with symptoms of an overexertion injury, most commonly pain and swelling in the affected muscles. Special attention should be given to evaluating the history for occupational, recreational, environmental and medical risk factors for rhabdomyolysis. Screening may be performed with a simple urine dipstick test; if the urine is orthotoluidine-positive, the diagnosis should be confirmed with measurement of the serum creatine kinase level. Early intervention with aggressive hydration and close monitoring for metabolic, renal or hematologic complications may prevent serious injury or death.