Apoptosis is a well-conserved cellular destructive event which has been implicated in a variety of diseases such as cancers and neurodegenerative diseases. The comprehensive investigation of apoptosis has been emerged in the field of skeletal muscle biology. Results have been consistent in demonstrating the activation of apoptotic machinery in different pathologic and physiologic muscle atrophic conditions including muscle disuse, hindlimb unloading, muscle dystrophy, sarcopenia, and neuromuscular diseases. Together with the other identified muscle atrophy-related signaling mechanisms such as NFκB, FOXOs/MuRF1/MAFbx and ubiquitin-proteasome, apoptosis has been advocated as an important candidate in regulating denervation-induced muscle loss. The purpose of this article is to review the role and signaling mechanisms of apoptosis during denervation in skeletal muscle including myofibers and satellite cells.