Elevated plasma total homocysteine is an independent risk factor for atherosclerotic vascular disease. Risk rises continuously across the spectrum of homocysteine concentrations and may become appreciable at levels greater than 10 mumol/l. A compelling case can be made for screening all individuals with atherosclerotic disease or at high risk. A reasonable, but unproven, goal for treatment is a plasma total homocysteine concentration less than 10 mumol/l. Folic acid is the mainstay of treatment, but vitamins B12 and B6 may have added benefit in selected patients. The results of ongoing randomized placebo-controlled trials will not be available for several years, but will help determine whether homocysteine lowering reduces the risk of cardiovascular disease.