Peripheral artery disease (PAD) is one of the most important causes of cardiovascular morbidity and mortality and its prevalence is alarmingly increasing in modern societies. PAD shares common characteristics with the other atherosclerotic diseases but involves specifically the arteries of the lower extremities. Apart from the changes in lifestyle, antiplatelet agents are the hallmark of the treatment and improve the symptoms as well as the progression of the disease. Aspirin is the cornerstone of treatment and is administrated in doses ranging from 75 to 325 mg daily. Additionally, cilostazol and clopidogrel have an important therapeutic role too. Novel antiplatelet agents are the subject of research in both experimental and clinical studies in order to evaluate the efficacy and safety profile. The most important antiplatelet factors which are under investigation are the novel P2Y12 receptor inhibitors prasugrel and ticagrelor. Furthermore, vorapaxar, a protease-activated receptor inhibitor, exhibits antiplatelet properties and has been studied in PAD.