The metabolic fate of homocysteine is linked to vitamin B12, reduced folates, vitamin B6 and sulfur amino acids. Clinical and experimental data suggest that elevated plasma homocysteine is an independent risk factor for premature vascular disease. This is particularly significant because plasma homocysteine levels are altered in several diseases, including folate and vitamin B12 deficiencies, and because many commonly used drugs have now been shown to interfere with homocysteine metabolism. In summarizing the data, Helga Refsum and Per Ueland highlight the clinical implications for these metabolic changes.