Infection of an aortic prosthetic graft represents one of the most difficult diagnostic and therapeutic challenges to the vascular surgeon. The presentation of this complication, the degree of ischemia of the lower extremities, and the overall medical status of the patient determine the urgency and optimal treatment to maximize limb salvage and survival. Although partial or total graft preservation can be a treatment option if the infection is localized to the distal limb of an aortofemoral graft and all anastomoses are intact, treatment of an infected aortic prosthetic graft often requires total graft excision, preferably preceded by revascularization of the lower extremities through lateral uninfected routes. Careful selection of the many time-honored and newly developed diagnostic and treatment modalities is necessary to lower morbidity and mortality rates in patients with this complication.