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Fatigue is an experience of our daily life, but its definition is very complex, not unique and controversial. In common language, fatigue may be described as a feeling or sensation of weakness or muscle pain or a decrement of performance, not easily suitable for quantification or measurement. In this chapter a possible approach to quantitative measurement of fatigue is described. The approach is based on the analysis of the surface EMG signal in the time and spectral domains. Indexes of fatigue are defined on the basis of the time evolution of the surface EMG signal features during the contraction. In this way fatigue can be assessed since the very beginning of a muscle effort. The indication pro-