Continuing widespread use of autologous saphenous vein for coronary artery bypass grafting seems unavoidable despite its poor-term patency. We review here the evidence that platelet activation is responsible for early and late vein graft occlusion and conclude that other mechanisms probably contribute to late occlusions. We suggest that a rational strategy to improve vein graft patency should include: improved endothelial preservation during surgical implantation; use of better antiplatelet agents, in particular those which prevent platelet adhesion as well as aggregation; reduction of risk factors including serum cholesterol; and application of agents (e.g. heparin) which inhibit smooth muscle cell proliferation directly. We draw parallels between the pathogenesis of vein graft occlusion and coronary atherosclerosis and suggest that testing strategies for improving vein graft patency may also shed light on atherogenesis.