Skeletal muscle cramps are commonly encountered in marathon runners by medical staff. However, the aetiology, and therefore management, of this condition is not well understood. Exercise-associated muscle cramping (EAMC) is defined as an involuntary, painful contraction of skeletal muscle during or immediately after exercise. In early anecdotal reports, cramps were associated with profuse sweating, together with changes in serum electrolyte concentrations. No mechanism explains how such imbalances in serum electrolytes result in localised muscle cramping. The 'muscle fatigue' hypothesis suggests that EAMC is the result of an abnormality of neuromuscular control at the spinal level in response to fatiguing exercise and is based on evidence from epidemiological studies, animal experimental data on spinal reflex activity during fatigue and electromyogram data recorded during bouts of acute cramping after fatiguing exercise. The development of premature muscle fatigue appears to explain the onset of EAMC.