Hyperhomocysteinaemia has been identified from epidemiological studies as an independent risk factor for cardiovascular disease. Plasma total homocysteine is elevated in renal impairment, which may be a consequence of cardiovascular disease. However, it is also likely that plasma total homocysteine promotes cardiovascular disease, particularly through effects on endothelial function and coagulation pathways. It is influenced by complex interactions between B-group vitamins, especially folate, and polymorphisms in various genes involved in homocysteine metabolism. Supplementation with folate and other B-group vitamins effectively lowers total plasma homocysteine and improves endothelial function. The results of clinical trials to assess effects on cardiovascular morbidity and mortality are awaited.