Apolipoprotein (apo) A-I, because of its anti-atherogenic properties, represents a powerful approach to the management of vascular diseases. Infusion of apoA-I-containing synthetic high-density lipoprotein (HDL) inhibits atherosclerosis progression or prevents restenosis in experimental animals, and apoA-I liposomes are capable of stimulating reverse cholesterol transport in humans. Moreover, many experimental studies have been conducted with a molecular variant of apoA-I, apoA-I(Milano), characterized by a prolonged residence time in plasma and improved function, which may offer an even better approach to the therapeutic handling of arterial disease.