A raised plasma level of the amino acid homocysteine is associated with increased risk of cardiovascular disease. This association may be causal-it is biologically plausible, fairly strong, graded, and an increase in plasma homocysteine preceeds the onset of vascular disease. Plasma homocysteine levels are controlled by genetic and nutritional factors, notably folate, vitamin B12 and vitamin B6 intakes. Folic acid in particular lowers plasma homocysteine levels by about 25%. It is not known if this cheap and safe treatment reduces vascular disease risk. Current randomized control trials are addressing this issue, and proof or otherwise of causality must await their results. Homocysteine may also interact with conventional risk factors such as smoking to substantially increase their effect on risk. Thus meticulous risk factor control may be particularly important in subjects at high total cardiovascular risk who also have a raised plasma homocysteine level, and folic acid supplementation may be considered in such individuals.