Intimal hyperplasia is central to the pathology of vein graft re-stenosis, and despite considerable advances in our understanding of vascular biology since it was first described 100 years ago, it is still a significant clinical problem. Recent decades have seen the development of many new therapeutic agents aimed at treating this condition, but the successes of laboratory studies have not been replicated in the clinic yet. This review discusses these therapeutic agents, how their modes of action relate to the pathogenesis of vein graft intimal hyperplasia, and considerations of ways in which such therapy may be improved in the future.