Normal pregnancy is associated with changes in the cardiovascular system, including vascular remodeling of the uterine and systemic circulation in order to meet the metabolic demands of the developing fetus. These cardiovascular changes are due to alterations in the amount/activity of vascular mediators such as nitric oxide, prostacyclin and endothelin in the endothelium; calcium and protein kinase C in the smooth muscle; and metalloproteases in the extracellular matrix. Hypertension in pregnancy is a major complication, and can lead to life threatening neurovascular disorders. It has been suggested that hypertension in pregnancy may develop from an inadequate invasion of cytotrophoblasts into the uterine artery, causing reduction in the uteroplacental perfusion pressure, and resulting in placental ischemia/hypoxia. This placental hypoxic state is thought to induce the release of various biologically active factors such as cytokines, reactive oxygen species, and hypoxia-inducible factors. Elevated plasma/tissue levels of these factors during pregnancy could cause vascular dysfunction, vasoconstriction and hypertension. The purpose of this review is to discuss the interactions between biologically active circulating factors and vascular mediators, released during preeclampsia as compared to those released in other conditions characterized by hypoxia, in order to provide insight into the sequence of events that leads to the development of hypertension in pregnancy.