This brief review discusses an exciting area in skeletal muscle research, namely the role of apoptosis in relation to muscle activity. Apoptotic cell death appears to occur during atrophy as a mechanism for removing part of the myofiber without affecting its viability. Recent developments in our understanding of the signaling of muscle catabolism and new insights into the therapeutic outlets are highlighted. The roles of mitochondria, Ca2+, and tumor necrosis factor alpha in activating the caspase cascade are discussed. We speculate that atrophy-induced apoptosis is a normal regulatory process that the cell can use to reduce the number of organelles, thus ensuring optimal cell function.