Cardiovascular disease is the leading cause of death in Western countries. Since 1969, homocysteine has been implicated in the atherosclerotic process, and numerous observational studies have suggested that hyperhomocysteinaemia should be considered as an independent cardiovascular risk factor. B-vitamins, particularly folic acid, reduce homocysteine levels effectively; it was suggested, therefore, that supplementation with these vitamins might decrease cardiovascular risk and reduce the morbidity and mortality associated with stroke, coronary heart disease and peripheral artery disease. However, the results of clinical trials conducted to investigate this issue have been inconsistent. This review discusses the findings of these trials and provides an updated overview on the 'homocysteine hypothesis'.