Rhabdomyolysis is the clinical and laboratory syndrome resulting from skeletal muscle injury and release of potentially toxic substances into the circulation. The severity of rhabdomyolysis varies widely from asymptomatic elevation of muscle enzymes to the life-threatening complications of acute renal failure and severe electrolyte abnormalities. The etiology of rhabdomyolysis may be considered under 4 categories: (1) trauma or direct injury, (2) excessive muscle activity, (3) hereditary muscle enzyme defects, and (4) other less obvious medical causes. The latter medical causes may be subdivided into the following: (1) drugs and toxins, (2) muscle hypoxia, (3) metabolic and endocrine disorders, (4) infections, (5) temperature alterations, and (6) miscellaneous causes. The diagnosis of rhabdomyolysis depends on recognizing the symptoms of muscle pain and weakness, detecting the presence of or history of red-to-brown urine (myoglobinuria), and finding short-term elevations of creatine kinase that are not attributable to myocardial infarction or inflammatory myopathies. The major therapeutic goal is to recognize and treat complications as soon as possible, particularly electrolyte abnormalities and acute renal failure. Knowledge of the other medical causes of rhabdomyolysis allows one to identify and treat this potentially serious condition in otherwise occult cases.