Vascular access dysfunction, due to venous stenosis at the vein-artery anastomosis in arteriovenous fistulas and vein-graft anastomosis in synthetic arteriovenous grafts, is a major cause of morbidity and mortality in dialysis patients. The two overarching approaches to prevent and treat vascular access dysfunction are from systemic or local (including endovascular and perivascular) routes. However, there are currently very few effective therapies to treat vascular access dysfunction. This article will review major studies evaluating systemic, endovascular, and perivascular therapies for vascular access dysfunction. Ongoing research to evaluate novel innovations to prevent and/or manage vascular access dysfunction appears promising.