An increase in the fasting plasma homocysteine concentration, even within the 'normal range', is a strong and independent predictor of cardiovascular risk. Low concentrations of specific B vitamins and decreased renal function are the most common causes of hyperhomocysteinaemia. Interventional trials with B vitamins showed a decrease in homocysteine levels, but no decrease in cardiovascular disease rates. There are several methodological concerns that preclude the drawing of definite conclusions from the trials; these include the fact that only very mild hyperhomocysteinaemia (>20 μmol/l) was investigated and that possible detrimental effects of high doses of synthetic folic acid were not excluded. Screening for hyperhomocysteinaemia is only indicated in patients with severe premature vascular disease or with indications for an inherited disorder in homocysteine metabolism. Treatment of hyperhomocysteinaemia with moderately high doses of B vitamins should only be considered in severe premature vascular disease or if concentrations are greatly elevated.