In industrialized nations, the leading cause of death and disability is atherosclerosis. Despite a widespread research effort spanning decades, there remains no clearly defined cause or cure for this disease that directly or indirectly affects the lives of almost all individuals in the western world. Autopsy findings show atherosclerosis to some degree in nearly all aged people, suggesting it should be regarded as a normal aging process as well as a disease. Any investigation of atherosclerosis etiology therefore requires a distinction between atherosclerosis normally observed with aging, and pathologic atherosclerosis causing disease and/or death. Atherosclerosis is most appropriately regarded as a disease when associated with both rapid progression and clinical symptoms. Widely accepted risk factors for atherosclerotic disease include advanced age, diabetes, tobacco use, arterial hypertension, hypercholesterolemia, hypertriglyceridemia, decreased high-density lipoprotein, some hypercoaguable states, sedentary life-style, and elevated plasma homocysteine. The study of lipid metabolism has dominated research into atherosclerosis etiology for decades, although now it is widely recognized that a large number of people with symptomatic atherosclerotic disease have no detectable evidence of abnormal lipid metabolism and . Elevation in plasma homocysteine has also been widely studied as an independent risk factor for atherosclerosis. A description of the metabolism of homocysteine, its relationship to vascular disease, evidence supporting its role as an independent risk factor for atherosclerotic vascular disease, and the potential role of treatment will form the basis for this review.