The potent vasodilator endothelium derived relaxing factor (EDRF) is released by the vascular endothelium both under basal conditions and upon stimulation by acetylcholine and other endothelium dependent vasodilators. EDRF has been identified as nitric oxide (NO) and provides communication between endothelial and smooth muscle cells in the vascular wall. Injured and/or dysfunctional endothelium as seen in a variety of cardiovascular diseases may result in decreased production of NO leading to unfavorable vasoconstriction and vasospasm whereas its overproduction may cause pathological vasodilation. Understanding the role of nitric oxide in regulation of vascular tone may facilitate novel strategies for prevention and treatment of cardiovascular disorders.