Improvements in manufacturing and implantation techniques, coupled with an increasing prevalence of atherosclerosis in an aging population, have led to increased utilization of prosthetic vascular grafts. The infection rates of vascular grafts are low. However, when they do occur, high rates of morbidity and mortality can be expected. The purpose of this article is to review the published literature regarding epidemiology, risk factors, pathogenesis, and clinical manifestations of prosthetic vascular graft infections. Moreover, we provide a practical approach to the diagnosis and management of these complicated infections based on empirically grounded evidence.