This brief review focuses on experimental studies linking the proinflammatory cytokine tumor necrosis factor-alpha to accelerated vein graft failure in the broader historical context of vein graft research. From some perspectives, the field appears ripe for transfer of cytokine knowledge and therapeutic approaches that have evolved in other systems to vascular surgery problems. However, the complexity of vein graft disease suggests that more robust research approaches, such as broadening of the scope beyond focus on single mediators and neointimal hyperplasia, will be necessary to reach translatable strategies to prolong human vein graft durability.