Skeletal muscle fibers and placental villous trophoblast are the main representatives of syncytia in the human. Both syncytia are derived from fusion of mononucleated stem cells, show a high degree of differentiation, and have lost their generative potency. Consequently, for their growth both depend on fusion of additional stem cells. There is evidence that syncytial fusion is directly or indirectly related to apoptotic events: As early as in the differentiated stages of the mononucleated stem cells, initiation stages of the apoptosis cascade have been observed. After syncytial fusion progression of the cascade is retarded or blocked by a variety of mechanisms. In this review we emphasize the links between apoptosis cascade, differentiation pathways and syncytial fusion. It needs to be elucidated whether these processes simply take place in parallel, both temporally and spatially, or whether there are causal connections between apoptosis cascade and syncytial fusion. Based on recent data obtained for placental villous trophoblast, it is tempting to speculate that early molecular mechanisms of the apoptosis cascade are involved in differentiation and syncytial fusion. Data obtained in skeletal muscles support this assumption and reveal a considerable degree of homology in genesis, maintenance and turnover of both tissues.