Homocysteine is increasingly recognized as a risk factor for coronary artery disease. An understanding of its metabolism and of the importance of vitamins B6 and B12 and folate as well as enzyme levels in its regulation will aid the development of therapeutic strategies that, by lowering circulating concentrations, may also lower risk. Possible mechanisms by which elevated homocysteine levels lead to the development and progression of vascular disease include effects on platelets, clotting factors and endothelium. This review presents the clinical and basic scientific evidence supporting the risk and mechanisms of vascular disease associated with elevated homocysteine concentrations as well as the results of preliminary therapeutic trials.