Hyperhomocyst(e)inemia is under scrutiny as a novel risk factor for atherosclerotic disease in the coronary, cerebral, and peripheral arterial circulations. It also appears to be a risk factor for venous thromboembolism. Low dietary intake of vitamins B(6) and folic acid is the most prevalent cause of hyperhomocyst(e)inemia. A critical unresolved question is whether hyperhomocyst(e)inemia itself, or alternatively some other effect of low vitamin levels, is the true determinant of excess cardiovascular risk. This issue is currently being addressed by prospective epidemiologic studies. There is also an urgent need for prospective randomized studies to determine whether vitamin supplementation is beneficial in the primary or secondary prophylaxis of atherosclerotic disease. In the meantime, lifestyle modifications and vitamin supplementation to reduce plasma homocysteine levels can be recommended, because these are innocuous interventions that may well prove to be beneficial. Until there is definitive evidence that treatment of hyperhomocyst(e)inemia does in fact alter clinical outcomes, however, other therapies that possess the potential for greater toxicity cannot be justified.