During early pregnancy the placenta-derived extravillous trophoblast starts to invade the maternal uterus in order to regulate adequate blood flow and nutrient supply to the growing fetus. A unique set of events including plugging and remodelling of maternal vessels, regulation of oxygen levels, as well as the crosstalk with maternal decidual cells are thought to be precisely controlled by the invading extravillous trophoblasts. However, defects in these processes can lead to severe complications during pregnancy threatening the well-being of both the mother and the developing fetus. For instance incomplete trophoblast-associated invasion and arterial remodelling are associated with preeclampsia, the most common pregnancy-related complication. Moreover, failure in proper placental development and adequate fetal nutrition could be effective later in life, as growth-restricted neonates have a higher risk to develop adult onset of hypertension, heart disease and diabetes mellitus. Consequently, a detailed understanding of the mechanisms that underlie trophoblast invasion is thought to improve both diagnosis and treatment of various pregnancy-related disorders.