Hemodialysis vascular access dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population at a cost of well over $1 billion per annum. Venous stenosis (due to venous neointimal hyperplasia [VNH]) is the most common cause of polytetrafluroethylene PTFE) dialysis access graft and arteriovenous fistula (AVF) failure. Despite the magnitude of the clinical problem, however, there are currently no effective therapies for this condition. We and others have previously demonstrated that VNH in PTFE dialysis grafts and AVF is composed of smooth muscle cells/myofibroblasts, endothelial cells within neointimal microvessels, and peri-graft macrophages. Radiation therapy blocks the proliferation and activation of all these cell types. The current review will dissect out the available in vitro, experimental, and clinical data on the use of radiation therapy for vascular stenosis in general, and for dialysis access dysfunction in particular. It is important to try and identify whether there is still a role for radiation therapy in this specific clinical setting. We believe that this is a critically important question to answer in view of the huge unmet clinical need that is currently associated with hemodialysis vascular access dysfunction.