Apoptosis — in concert with proliferation — in any tissue keeps the number of cells constant by eliminating cells which are damaged, overaged or simply have lost their significance for the tissue. Accordingly, apoptosis is important for the homeostasis of adult tissues and organs. During fetal development it is involved in morphogenesis of all organs by eliminating cells, resulting in the formation of clefts or lumina (e.g., limbs, gut, heart) or by participating in the involution of structures (e.g., müllerian duct in male fetuses) (Erickson, 1997; Jacobson et al., 1997).The morphological signs of apoptosis comprise cellular shrinkage, membrane blebbing, nuclear condensation as well as nuclear and cellular fragmentation. These signs are the result of a complex biochemical cascade of events. Some of the steps of apoptosis are indispensably linked to processes of differentiation. Analysis of these links requires investigation not only of the final stages of apoptotic death (e.g., TUNEL test); rather morphological visualization of earlier stages is required.It is the intention of this article to outline those stages of the proposed mainstream of the apoptosis cascade which can be studied morphologically, and to correlate these stages with differentiation and turnover of villous trophoblast in the human placenta. The stages comprise (a) induction of apoptosis by specific ligands and receptors, (b) early, still reversible stages of apoptosis including degradation of the cytoskeleton, blebbing and phosphatidylserine flip, (c) inhibition of further progression of the cascade at least for a limited time-span by means of regulatory mitochondrial proteins, (d) irreversible execution of the cascade by cleavage of a variety of cytoplasmic and nuclear proteins and breakdown of nuclei acids, and (e) the final events of apoptotic death.The data obtained allow a deeper understanding of differentiation and turnover of the villous trophoblast including its syncytial fusion.