Arteriovenous access failure is multifactorial in nature with contributions from both medical and surgical etiologies. Medical causes of arteriovenous access failure are rare, and therefore infrequently identified as a major contributing source of malfunction. Although they account for only 10-15% of all cases of access failure, their importance should not be underestimated, especially in cases where a surgical source cannot be identified. Most medical causes are derived from Virchow's triad of endothelial cell injury, stasis, and hypercoaguability. Endothelial cell injury occurs through oxidative stress, activated platelets, increased levels of circulating tumor necrosis factor-alpha, and preexisting intimal hyperplasia. Stasis can occur through prolonged access compression, hypotension, or hypoalbuminemia. Finally, patients with renal failure requiring hemodialysis are frequently at increased risk for hypercoaguable states, except for situations of platelet dysfunction, and therefore access failure. Potential treatments include identifying and removing the offending source, as well as innovative, new medications to prevent their reoccurrence. Treatment is aimed at improving quality of life, as well as decreasing morbidity and hospital admissions in this difficult patient population.