For patients with the most severe manifestations of lower extremity arterial occlusive disease, bypass surgery using autogenous vein has been the most durable reconstruction. However, the incidence of bypass graft stenosis and graft failure remains substantial and wholesale improvements in patency are lacking. One potential explanation is that stenosis arises not only from over exuberant intimal hyperplasia, but also due to insufficient adaptation or remodeling of the vein to the arterial environment. Although in vivo human studies are difficult to conduct, recent advances in imaging technology have made possible a more comprehensive structural examination of vein bypass maturation. This review summarizes recent translational efforts to understand the structural and functional properties of human vein grafts and places it within the context of the rich existing literature of vein graft failure.