Exercise Associated Muscle Cramps (EAMC) is one of the most common conditions that require medical attention during or immediately after sports events. Despite the high prevalence of this condition the etiology of EAMC in athletes is still not well understood. The purpose of this review is to examine current scientific evidence in support of 1) the “electrolyte depletion” and “dehydration” hypotheses”, and 2) the “altered neuromuscular control” hypothesis in the etiology of EAMC. In this review, scientific evidence will, as far as possible, be presented using evidence based medicine criteria. This is particularly relevant in this field, as the quality of experimental methodology varies considerably among studies that are commonly cited in support of hypotheses to explain the etiology of EAMC. Scientific evidence in support of the “electrolyte depletion” and “dehydration” hypotheses for the etiology of EAMC comes mainly from anecdotal clinical observations, case series totaling 18 cases, and one small (n=10) case-control study. Results from four prospective cohort studies do not support these hypotheses. In addition, the “electrolyte depletion” and “dehydration” hypotheses do not offer plausible pathophysiological mechanisms, with supporting scientific evidence that could adequately explain the clinical presentation and management of EAMC. Scientific evidence for the “altered neuromuscular control” hypothesis is based on evidence from research studies in human models of muscle cramping, epidemiological studies in cramping athletes, and animal experimental data. Whilst it is clear that further evidence to support the “altered neuromuscular control” hypothesis is also required, research data are accumulating that support this as the principle pathophysiological mechanism for the etiology of EAMC.