Nitric oxide synthase (NOs) is an enzyme family that converts L-arginine into citrulline with the formation of an oxygen reactive intermediate, nitric oxide. This volatile compound can exist under three redox forms: nitric oxide radical, nitrosonium cation and nitroxyl anion with different chemical-physical properties. In skeletal muscle the most representative isoform which is typical of the nervous system (ncNOs) and about 90% of its activity is related to the dystrophin-glycoprotein complex of sarcolemmal component. The first data concerning a possible NO implication in the regulation of skeletal muscle activity, were those of Balon and Nadler who demonstrated a direct correlation “in vitro” between a long time electrical stimulation and skeletal muscle NO production. More recently other authors have demonstrated several NO-dependent effects during muscular activity: cGMP-mediated relaxing effect in fast twitch fibres, a stimulating action on force generation, and opposite effects (depending of NO species) on terminal cisternae calcium channels. These and others possibilities are discussed.