Under basal conditions, nitric oxide (NO) modulates vascular tone, serves as an antithrombotic agent, and inhibits vascular smooth muscle cell proliferation. NO deficiency has been implicated in the pathophysiology of several vascular disorders, including hypertension, atherosclerosis, and restenosis, and provides a plausible biologic basis for the use of NO replacement therapy in these conditions. Treatment with conventional nitrate preparations is limited by a short therapeutic half-life, systemic absorption with potentially adverse hemodynamic effects, and drug tolerance. To overcome these limitations, novel delivery systems and novel NO donors have been developed that offer selective effects, a prolonged half-life, and a reduced incidence of tolerance.