It has been recognized, since the first description of the disease, that arterial and venous thrombosis are common in patients with homocysteinuria. Interest in the condition increased with reports from a large number of mainly retrospective studies showing that mildly elevated homocysteine levels are also associated with venous thromboembolism (VTE), thrombotic stroke, and peripheral vascular disease. This association is less strong when populations are studied prospectively. Vitamin supplementation, primarily with folic acid, and to a lesser degree with pyridoxine and vitamin B(12), is effective in reducing elevated levels of plasma homocysteine. Surprisingly, however, recent prospective intervention studies showed that despite lowering of the homocysteine level with such treatment, there was no impact on the risk of recurrence of venous or arterial disease.