Homocysteine is an intermediate compound formed during metabolism of methionine. The results of many recent studies have indicated that elevated plasma levels of homocyst(e)ine are associated with increased risk of coronary atherosclerosis, cerebrovascular disease, peripheral vascular disease, and thrombosis. The plasma level of homocyst(e)ine is dependent on genetically regulated levels of essential enzymes and the intake of folic acid, vitamin B6 (pyridoxine), and vitamin B12 (cobalamin). Impaired renal function, increased age, and pharmacologic agents (e.g. nitrous oxide, methotrexate) can contribute to increased levels of homocyst(e)ine. Plausible mechanisms by which homocyst(e)ine might contribute to atherogenesis include promotion of platelet activation and enhanced coagulability, increased smooth muscle cell proliferation, cytotoxicity, induction of endothelial dysfunction, and stimulation of LDL oxidation. Levels of homocysteine can be reduced with pharmacologic doses of folic acid, pyridoxine, vitamin B12, or betaine, but further research is required to determine the efficacy of this intervention in reducing morbidity and mortality associated with atherosclerotic vascular disease.