Skeletal muscle makes up the largest organ of the body, by both volume and weight, comprising more than 40 %. More than 500 diseases concern muscle tissue, the majority of which originate in muscle, others secondarily affect the muscle, foremost by denervation. The functional and structural dependence of skeletal muscle on innervation—that is, the peripheral and central nervous systems—renders muscle tissue unique and adds a dimension to the nosology, more obviously than in other organs. Therefore, diseases affecting muscle are also termed neuromuscular diseases. Within the nosological spectrum of the muscle parenchyma, which encompasses hereditary and acquired conditions, muscular dystrophies, channelopathies, congenital myopathies, and inflammatory and metabolic disorders, malformations and neoplasms are strikingly absent. Vascular pathology rarely affects skeletal muscle whereas endocrine pathology may do so.