Normal pregnancy is associated with decreased peripheral vascular resistance, although the mechanisms are poorly understood. Pre-eclampsia is characterised by increased vessel resistance and a decreased relaxant capacity, contributing to the associated hypertension, multi-organ damage and intra-uterine growth restriction. An endothelium-derived vasoactive substance-endothelium-derived hyperpolarising factor may be responsible for the physiological changes in the maternal vasculature. This is a review of the current understanding of the complexities of vessel behaviour. Evidence is reviewed to support the possible contribution of endothelium-derived hyperpolarising factor to the compromised vascular state in pre-eclampsia. This is an important area of research which may help to understand further the pathogenesis of this specific pregnancy related disease, that contributes greatly to maternal and fetal morbidity and mortality.