Preeclampsia is a hypertensive disorder unique to human pregnancy that can result in significant morbidity and mortality for mother and fetus. While the etiology of preeclampsia is unknown, the placenta in general and trophoblast in particular is a prerequisite for the disease. We overview normal development of the human placenta, describe the role of hypoxia and other insults in placental injury, and highlight how the dysregulation of villous trophoblast biology in the second half of pregnancy may incite the pathophysiology of preeclampsia in the mother.