The maternal cardiovascular adaptation to pregnancy involves a complex physiologic response to the presence of the growing conceptus, including alterations in maternal vascular endothelial cells that contribute to a profound fall in total systemic vascular resistance. There is a large body of evidence that adverse changes in the vascular endothelium underlie the multisystemic maternal manifestations of preeclampsia. Our knowledge is incomplete regarding the mechanisms of adaptive endothelial changes of normal pregnancy and why these changes are attenuated or fail in women who develop preeclampsia. Populations of bone-marrow derived endothelial progenitor cells (EPCs) exist in the adult that are mobilized into the circulation by stimuli such as estrogen and vascular endothelial growth factor. These EPCs can then differentiate into endothelial cells lining the lumen of blood vessels and/or release growth factors that act in a paracrine fashion to support the endothelium. EPCs are thus thought to function as a cellular reservoir to replace dysfunctional or senescent endothelial cells, and therefore may be critical to the overall health of the vascular endothelium. Data are emerging to suggest that the number of EPCs in the maternal circulation increases with normal pregnancy and that this change fails to occur in women with preeclampsia. While speculative at this point, our overall hypothesis is that an excess of antiangiogenic factors [such as the soluble receptors, soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin] interfere with nitric oxide-driven mobilization or activity of EPCs in the maternal circulation, contributing to the widespread endothelial dysfunction underlying the clinical manifestations of preeclampsia.