Several clinical conditions related to womens cardiovascular health strongly correlates with endothelial dysfunction, which is conventionally associated with alterations in synthesis, release or bioavailability of endotheliumderived nitric oxide (NO). Current review pays attention to rapidly growing evidence about the importance of Endothelium-Derived Hyperpolarizing Factor (EDHF). EDHF-mediated action is pertinent to resistance circulation where EDHF overcomes NO contribution, while in large conduit vessels endothelium-dependent dilatation is predominantly conferred by NO. This indicates that changes in synthesis, release, or pharmacological manipulation of EDHF is of critical importance in the maintenance of organ perfusion, peripheral resistance and blood pressure, the disturbances in which distinctively predispose the development of cardiovascular disorders. This review describes current knowledge about EDHF, including nature and characterization of its action, alterations in the mechanisms of EDHF contribution to endothelium-dependent relaxation with particular focus on preeclampsia, gender differences and cardiovascular complications after menopause. The distinction in the relative contribution of NO versus EDHF and estrogen-related regulation of EDHF-mediated responses are highlighted. The indications that EDHF-mediated response accounts for different chemical mediator or electrical transmission depending on species, vascular bed and healthy or diseased condition are discussed paying attention to womens cardiovascular health and future therapeutic implications.