The placenta has evolved as a specialized organ in a subgroup of mammals to enable the prolonged intrauterine development of the fetus. It is a gender-specific and transitory organ that is essential for the exchange of nutrients and metabolites between the circulatory systems of the mother and fetus. The vascular bed of the placenta is established de novo at the onset of pregnancy, and regresses after delivery. The tissue mass of the placenta comprises both maternal and fetal elements. As a result of the so-called hemochorial type of placentation observed in humans, the vascular space containing maternal blood in the placenta is lined by two different types of cells: endothelial cells (ECs) of maternal origin and trophoblast cells of fetal origin. On the other hand, fetal blood vessels emanating from the embryo/fetus into the placental tissue remain intact, and fetal and maternal blood therefore remains segregated. Thus, whereas in all other vascular beds the blood vessel endothelium is the principal gatekeeper between tissue and blood, in the placenta a different cell type, the trophoblast cell, occupies part of the interface between (maternal) blood and (fetal) tissue. By their particular anatomical position at the bloodtissue boundary, trophoblast cells are equivalent to ECs in other organs, and fulfill EC-like functions. The concept of endothelial mimicry by trophoblast cells was initially coined to describe a remarkable process of remodeling of the maternal arteries supplying blood to the placenta, during which socalled endovascular fetal trophoblast cells replace the maternal endothelium in these arteries and induce an erosion of smooth muscle cells regulating the vascular tone of these arteries.