Pregnancy encompasses substantial changes in vascular function to accommodate dramatic increases in blood volume and uteroplacental blood flow to the growing fetus. Despite increased hemodynamics, decreased peripheral resistance results in a reduction in mean arterial blood pressure. Vascular tone, and hence peripheral resistance, is determined by a delicate balance of constrictor and dilator capacities. In the normal physiological response to pregnancy, endothelial-derived hyperpolarization (EDH) has been shown to be a major contributor; both EDH and nitric oxide (NO) are predominantly involved in providing an increased vascular capacity for vasodilation. The ability of EDH and NO to adequately accommodate increased blood volume is tested in pathological states such as placental insufficiency or diabetes and both EDH and NO-dependent mechanisms seem to be impacted in these situations. Pregnancy complications also have an impact on the cardiovascular health of the offspring. In adult offspring born from complicated pregnancies, the data suggest that EDH mechanisms are largely maintained, whereas NO is commonly reduced. A diversity of EDH mechanisms may be useful in providing many targets for potential therapeutic avenues for compromised pregnancies; however, further research delineating the mechanisms of EDH and the interactions of NO and EDH, in normal and pathological pregnancies is required.