Muscle cramp is a common, painful, physiological disturbance of skeletal muscle. Many athletes are regularly frustrated by exercise-induced muscle cramp yet the pathogenesis remains speculative with little scientific research on the subject. This has resulted in a perpetuation of myths as to the cause and treatment of it. There is a need for scientifically based protocols for the management of athletes who suffer exercise-related muscle cramp. This article reviews the literature and neurophysiology of muscle cramp occurring during exercise. Disturbances at various levels of the central and peripheral nervous system and skeletal muscle are likely to be involved in the mechanism of cramp and may explain the diverse range of conditions in which cramp occurs. The activity of the motor neuron is subject to a multitude of influences including peripheral receptor sensory input, spinal reflexes, inhibitory interneurons in the spinal cord, synaptic and neurotransmitter modulation and descending CNS input. The muscle spindle and golgi tendon organ proprioceptors are fundamental to the control of muscle length and tone and the maintenance of posture. Disturbance in the activity of these receptors may occur through faulty posture, shortened muscle length, intense exercise and exercise to fatigue, resulting in increased motor neuron activity and motor unit recruitment. The relaxation phase of muscle contraction is prolonged in a fatigued muscle, raising the likelihood of fused summation of action potentials if motor neuron activity delivers a sustained high firing frequency. Treatment of cramp is directed at reducing muscle spindle and motor neuron activity by reflex inhibition and afferent stimulation. There are no proven strategies for the prevention of exercise-induced muscle cramp but regular muscle stretching using post-isometric relaxation techniques, correction of muscle balance and posture, adequate conditioning for the activity, mental preparation for competition and avoiding provocative drugs may be beneficial. Other strategies such as incorporating plyometrics or eccentric muscle strengthening into training programmes, maintaining adequate carbohydrate reserves during competition or treating myofascial trigger points are speculative and require investigation.