Homocyst(e)ine is a novel risk factor in vascular disease. First observations of vascular lesions in children with high blood homocyst(e)ine levels due to severe inborn enzyme deficiencies led to the hypothesis that elevated blood homocyst(e)ine levels might be a risk factor for vascular disease. A substantial body of evidence on the role of the homocyst(e)ine in the development of coronary and carotid artery disease, myocardial infarction, stroke, deep vein thrombosis and other disorders has been accumulated over the last 30 years. Cross-sectional and case-control studies provide initial and the strongest support for the hypothesis, followed by results from the prospective cohorts. Infrequent cases of homozygous mutations of the key enzymes in the homocyst(e)ine metabolism chain are able to produce extreme homocyst(e)inemia and early vascular lesions. More frequently, heterozygous enzyme mutations and deficiencies of folate and vitamins B6 and B12 cause mild to moderate homocyst(e)inemia, which is still strongly associated with the increased risk of vascular events. Elevated homocyst(e)ine levels may be effectively managed with adequate folate, B12 and B6 intake in doses comparable to or above FDA recommendations. Whether correction of elevated homocyst(e)ine levels with vitamins is helpful in prevention and treatment of vascular events remains unknown and is under investigation in ongoing clinical trials (VISP, VITATOPS). No consensus on homocyst(e)ine management is available at the present time. (C) 2003 Prous Science. All rights reserved.