Saphenous vein grafts (SVGs) are the most widely used conduit in coronary artery bypass grafting (CABG) surgery; however, SVG failures due to neointimal hyperplasia present a significant long-term limitation to the effectiveness of myocardial revascularization. This review will provide a comprehensive overview of the biological mechanisms of vein graft failure, including compensatory endothelial proliferation, extracellular matrix deposition, and adventitial disruption. We will discuss historical and emerging strategies for vein graft failure prevention with a focus on the role of mechanical vein graft support using external stenting. Finally, we will highlight the results of preclinical and human trials and discuss future directions for investigation.