Proper medical management may enhance perioperative and long-term outcomes for patients with peripheral arterial disease (PAD). For patients with PAD, aspirin and statin drugs remain the mainstay of medical management, based on results from multiple randomized clinical trials that have demonstrated improvements in long-term survival and a decrease in cardiovascular events with these agents. There may additional, unintended positive consequences of treatment with statin drugs, including potential improvements in symptoms of claudication and enhanced graft patency after infrainguinal bypass. For patients undergoing surgical or endovascular revascularization, aspirin remains the standard of care for antithrombotic therapy. Beyond this, use of warfarin should be reserved for patients with high-risk surgical bypass grafts to prolong graft patency, because it carries a significant risk of bleeding complications. The utility of clopidogrel after surgical and endovascular infrainguinal revascularization remains undefined but warrants additional study. At this time the only clear indication for clopidogrel in patients with infrainguinal arterial occlusive disease is for PAD patients who are intolerant of aspirin or have a history of coronary artery stenting within the past 6 months. Proper adjunctive pharmacotherapy for the patient with PAD has the potential to improve symptoms, graft patency, and survival in this challenging subset of patients.