Trophoblast invasion is a key process during human placentation. This event constitutes the basis of the conversion of the uterine spiral arteries, a process which allows an adequate vascular connection between the intervillous space and the maternal blood flow. Trophoblast invasion is transient, with stringent spatial and temporal control. Preeclampsia, a leading cause of maternal and fetal mortality and morbidity, is associated with decreased, shallow trophoblastic invasion. In this article, we review the molecular mechanisms of trophoblast invasion, and its mechanisms of regulation. Insights into the etiopathogenesis of preeclampsia will also be detailed.