Saphenous vein grafts used in coronary artery bypass graft surgery suffer from lower patency rates of long term compared with left internal mammary artery and radial artery. A number of clinical trials and observational studies have demonstrated a significant benefit of statin treatment on vein graft patency. Statins exert pleiotropic effects by direct inhibition of the mevalonate pathway in the wall of these grafts. This leads to reducing geranylgeranylation of small GTPases such as Rho and Rac. Through this LDL-independent mechanism, statins can improve endothelial function and reduce vascular inflammation and oxidative stress, and inhibit the proliferation and migration of smooth muscle cell. Although the existing evidence support a beneficial effect of statins on vein grafts biology, more clinical trials focused on the effect of aggressive statin treatment on vein graft patency are required, in order to safely translate this strategy into clinical practice. This article will make a discussion of the issues.