Apoptosis is a physiological, conserved program of cellular suicide, characterized by nuclear condensation, DNA-fragmentation and release of mitochondrial cytochrome c into the cytoplasm. The apoptotic program is executed by a cascade of highly specific caspases. The occurrence and significance of apoptosis in multinucleated, differentiated cells, like skeletal muscle cells is discussed controversy in the current literature. In this review we will summarize the knowledge concerning the occurrence of apoptosis in certain diseases and the regulation of apoptosis in skeletal muscle.