Muscle fatigue may take place anywhere from changes at or distal to the neuromuscular junction (peripheral fatigue) to a progressive reduction in voluntary activation of muscle during exercise (central fatigue) and focuses on any exercise-induced reduction in the ability of a muscle to generate force or power. Therefore, during dynamic muscle actions, an integrative approach will be required to aid in the determination and differentiation of peripheral and central aspects of fatigue. The decline in skeletal muscle force production that occurs during repetitive bout of repetitions to failure has been recently showed to be in part as a consequence metabolic depletion (i.e. 23 to 80% ATP, PCR and muscle glycogen decreases) and/or metabolic accumulation (i.e. up to 12 fold lactate, acid uric and blood ammonia increases). During repetitive dynamic contractions, frequency analysis of myoelectric signals [i.e., using the mean power spectral frequency (MNF)], undergoes a decrease in muscle power output that is significantly related to the change in MNF. Strenuous resistance exercise is also known to be a potent stimulus for acute increases in circulating anabolic hormones, as well as in a number of pro-inflammatory and anti-inflammation responsive cytokines (i.e. IL-6). The skeletal muscle is thus exposed to an elevated peripheral anabolic hormone concentration and cytokine response increasing the likehood of plausible interactions with muscle cell and/or tissue receptors, and thereby mediating in part exercise-related metabolic changes. This study was supported in part by a grant from the Ministerio de Educación y Ciencia, Plan Nacional de I+D+I 2004-2007, Spain(Grant DEP2006-56076-C06-01)