Nitric oxide signal transduction pathway has been detected in a number of cell types including vascular endothelial cells, smooth muscle cells, and noncholinergic nonadrenergic nerve endings. Nitric oxide synthase is a key enzyme which produces nitric oxide from L-arginine. Three different types of this enzyme have been described: constitutive soluble, inducible soluble, and constitutive particulate. Nitric oxide is a lipophilic molecule that can rapidly diffuse through biological membranes. It provides communication between endothelial and smooth muscle cells as well as between nerve endings and smooth muscle cells. Decreased production of nitric oxide may lead to vasospasm, whereas its overproduction may cause pathological vasodilatation. Understanding of the role of nitric oxide signal transduction pathway in regulation of vascular tone will facilitate design of better strategies for the prevention and treatment of vascular diseases.