There is occurring a progressive increase in peripheral arterial disease (PAD) in the United States and around the World. This is undoubtedly associated with deterioration in health status and an increase in cardiovascular risk factors. There are multiple old and new antithrombotic and anticoagulation medications that have been used for the treatment of PAD. Several are considered in this review. The purpose of antithrombotics in surgery is the prevention of thrombosis of surgical bypass grafts in order to help maintain their patency. Multiple different medication approaches can be made in association with surgery. Just as in the case of peripheral vascular surgery, thrombosis also plagues the long-term maintenance of patency following peripheral vascular interventions (PVIs). Platelets play a key role in the initiation and propagation of thrombus formation following these PVIs and the use of antithrombotic medication helps reduce the likelihood of intravascular thrombus formation and adverse ischemic events during and after the procedure. Currently used antithrombotic agents after percutaneous peripheral revascularization include aspirin, clopidogrel, cilostazol and warfarin. Available medications remain in a state of flux and new oral direct thrombin and Factor Xa inhibitors may also find a place as clinical evidence-based medicine accumulates.