Hyperhomocysteinemia is now recognized as a common risk factor for thrombotic vascular events such as stroke, myocardial infarction, and venous thrombosis. Studies of cultured cells in vitro indicate that homocysteine has prothrombotic effects on the endothelium and vascular smooth muscle. An association between moderate hyperhomocysteinemia and vascular dysfunction was confirmed in recent studies in animals and humans. Current models propose that dysregulation of homocysteine metabolism may impair vascular function through mechanisms involving oxidant stress or altered cellular methylation. Although moderate hyperhomocysteinemia can be treated effectively by administration of folic acid and other B vitamins, the clinical benefit of this therapeutic approach has not been proven in patients with thrombosis.