In addition to risk-factor modification, antithrombotic therapy is the hallmark of management to reduce cardiovascular ischemic events in patients with peripheral artery disease (PAD). Currently, the guidelines recommend long-term antiplatelet therapy with aspirin or clopidogrel in this patient population to reduce myocardial infarction, stroke, and vascular death. Past outcomes studies have shown some benefit of ticagrelor, another antiplatelet agent, as compared with clopidogrel in patients with coronary disease and concomitant PAD. However, most recently, the Examining Use of Ticagrelor in Peripheral Artery Disease (EUCLID) trial has shown no additional benefit of ticagrelor over clopidogrel. In this trial, a minority of patients had concomitant coronary artery disease, making it unique to previous studies. The EUCLID trial's evidence of neutrality between clopidogrel and ticagrelor sheds light into the complexity of studying the PAD population and the continued need to meticulously design trials to investigate the optimal therapies. The topics that will be discussed in this review include the role of antiplatelet therapy in the management of patients with PAD, a review of the EUCLID trial results and the important factors to be considered in interpreting the surprising results, and promising recent ongoing clinical trials assessing therapies in the treatment of patients with PAD.