Hyperhomocysteinemia, the pathological increase of plasma homocysteine concentrations, is gaining increased attention in atheroscierosis research. Reasons for the wide present interest for this disorder of metabolism are that it may account, in the hereditary heterozygous and the acquired forms, for a still undetermined but possibly very large number of clinical manifestations of atheroscierosis in the adult population; and that the current understanding of the mechanisms by which high plasma concentrations of homocysteine induce vascular damage is presently to a large extent incomplete. As indicated by several lines of evidence, the endothelial cell appears to be the main target for the sustained toxic aggression by hyperomocysteinemia, possibly through the generation of an enhanced oxidative stress. A better understanding of the causes and mechanisms of homocysteine-induced vascular damage will likely lead to the development of better targeted preventive and therapeutical approaches in vascular disease.