Conversion of the maternal spiral arteries into larger competent vessels is one of the essential steps in the development of the normal placenta. This process is apparently dependent on the invasion by trophoblasts of the sub-endometrial area and the spiral arteries. Preeclampsia is characterized by shallow trophoblast invasion and unconverted narrow spiral arteries. This leads to fetal hypoxia that causes endothelial injury that eventually manifest as maternal hypertension, edema, and proteinuria. The following steps have been shown to be involved in the breakthrough of the trophoblasts from the uterine cavity into the decidua and the spiral arteries: trophoblast targeting, adhesion, and detachment from the extracellular matrix (ECM), invasion of the ECM and maternal vessels by proteolysis. Abnormal expression and activity of these molecules may explain in part some of the molecular mechanisms leading to abnormal placentation and the development of preeclampsia.