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Fatigue can be defined as the failure to maintain an expected power output. This is often an antecedent to some sports-related injury. It is important for those involved in physical performance to be familiar with the variety of mechanisms which can lead to fatigue. All too often, a single factor is described as the cause of fatigue when actually fatigue may be a combination of factors that contribute to the sequence of events that results in decreased performance. It may be suggested that every step in the chain of events that leads to voluntary contraction of skeletal muscle could be a culprit in fatigue. Peripheral sites and processes include the motor neuron, neuromuscular junction, sarcolemmal membrane, excitation-contraction coupling, accumulation of metabolites, or depletion of fuels. Physical training is frequently designed to delay the onset of fatigue. The actual mechanism(s) add to the specificity concept, that is, a “specificity of fatigue”. To the performer, the end result is the same, the inability to maintain his or her expected level of performance or power output.