Muscle membrane injury is a predictable consequence of extreme exertion. The risk is compounded if an untrained individual performs eccentric exercise in a hot environment, or there is any preceding infectious disease, drug ingestion or an underlying metabolic disorder. Once the integrity of the membrane is breached, a constellation of physiological changes follows. Cell contents leak out and extracellular components leak in. Muscle pain and weakness ensue. Myoglobin is but one substance that is liberated into the bloodstream. When dehydration, hypovolaemia and acidosis are added to the myoglobin load, the kidney may respond by ceasing its excretory and metabolic functions. This is the most serious consequence of rhabdomyolysis, and may be life threatening. The clinical setting, in combination with laboratory features of a grossly elevated creatine kinase, orthotoluidine positive urine and granular casts provides a rapid and accurate means of diagnosis in most cases. Management principles include aggressive fluid replacement, early use of cation exchange resins and dialysis for electrolyte control, plus fasciotomy for relief of compartment syndrome and limb preservation. Following this protocol, the prognosis is excellent. Prior conditioning clearly reduces the incidence of exercise-related muscle injury. Future research should concentrate on the rate at which training loads can be safely increased.