atigue is a common phenomenon in many medical and neurologic diseases. Understanding the origins of fatigue in these diseases is of great guiding significance in developing targeted interventions for muscle fatigue. In this review, the central origin (including all the supraspinal and spinal physiological phenomena capable of inducing a decrease in motoneuron excitation) and the peripheral origin (including neuromuscular transmission, propagation of action potentials in muscle, excitation-contraction coupling) of muscle fatigue were summarized. The methods of assessing the central or peripheral origin of muscle fatigue were discussed, including the direct measurement (maximal voluntary contraction force, twitch force) and the indirect tests (twitch interpolation, electromyography, motor cortical stimulation).