Peripheral arterial disease (PAD) is well recognized as a marker for systemic atherosclerosis. Platelets play an essential role in all stages of the disease, contributing to both thrombosis and the development of atherosclerosis. Medication regimens to optimize outcomes in both patients who are to undergo revascularization and those who will be managed without interventional therapy must address antiplatelet therapy. Given the common cardiovascular and cerebrovascular comorbidities in patients with PAD, antiplatelet therapy has the potential to decrease thromboembolic events in addition to improving patency after interventions. This clinical update reviews the current literature and recommendations for antiplatelet therapy in patients with PAD.