Atherosclerosis is a leading cause of death and disability in the Western world, and an important risk factor for it may be an elevated level of the plasma amino acid homocysteine. The biochemical characteristics of homocysteine, along with historical, laboratory, and clinical evidence for its pathologic role in atherosclerosis, are reviewed. Possible therapies for reducing elevated homocysteine levels and the possible impact of therapy in atherosclerosis are examined.