The endothelium maintains vascular homeostasis through the release of active vasodilators. Although Nitric Oxide (NO) is recognized as the primary factor at level of arteries, increasing evidence for the role of another endothelium-derived vasodilator known as an endothelium-derived hyperpolarizing factor (EDHF) has accumulated in the last years. Experiments show that when NO and Prostacyclin (Vasodilators) are inhibited there is still another factor causing the vessels to dilate[1] Despite the ongoing debate of its intriguingly variable nature and mechanisms of action, the contribution of EDHF to the endothelium-dependent relaxation is currently appreciated as an important feature of “healthy” endothelium. Since EDHF's contribution is greatest at level of small arteries, the changes in the EDHF action are of critical importance for the regulation of organ blood flow, peripheral vascular resistance, and blood pressure, and in particular when production of NO is compromised. Moreover, depending on the type of cardiovascular disorders altered, EDHF responses may contribute to, or compensate for, endothelial abnormalities associated with pathogenesis of certain diseases. It is widely accepted EDHF plays an important role in vasotone, especially in microvessels. Its effect varies, depending on the size of the vessel.