L-arginine, a semi-essential amino acid, can enhance the synthesis of nitric oxide (NO) via the nitric oxide synthase pathway. Enhanced bioavailability of NO may prevent activation of pro-inflammatory endothelial genes by the inhibition of nuclear transcription factor NF 3B, thus preventing the expression of adhesion molecules on endothelial surfaces. Animal studies have demonstrated that the chronic administration of L-arginine reduces the extent of atherosclerosis and prevents xanthoma development in LDL receptor knockout mice. Human studies have demonstrated improvement in endothelium vasodilator function both in coronary arteries and forearm flow responses. In addition oral L-arginine reverses an increased monocyte-endothelial adhesion in men with coronary artery disease and normalizes platelet aggregation in hypercholesterolemic humans. L-arginine may be a promising drug in the therapy of atherosclerosis. (Int J Cardiovasc Interventions