Apoptosis is a tightly regulated biological process that plays an important role in coordinating cellular proliferation and differentiation. The pathological consequences of aberrant regulation of apoptosis have been widely demonstrated in carcinogenesis, neurodegenerative diseases, autoimmune diseases, viral infections, and acquired immunodeficiency syndrome. The study of apoptosis has been initiated in skeletal muscle biology. Consistent data have indicated the activation of apoptotic events in muscle atrophic conditions including neuromuscular diseases, muscle disuse, and sarcopenia. Although these results seem to link apoptosis to muscle atrophy, the causative role of apoptosis in this process still needs to be established. Further perspective studies are desired to reveal the precise mechanism and the exact physiologic role of apoptosis in muscle adaptation. This article aims to stimulate research into apoptosis in skeletal muscle. It reviews the apoptotic response of skeletal muscle to the atrophic conditions, namely, denervation, disuse, and aging, and discusses the proposed potential physiological links of apoptosis with muscle loss.