Cardiovascular disease is one of the major causes of death in developed countries, mainly related to coronary artery disease and its acute complications. Platelets play a great role in the pathogenesis of acute thrombotic events of coronary artery disease when silent chronic disease becomes acutely symptomatic. Platelet importance in coronary artery disease and pathophysiology of acute events support the large benefit of antiplatelet agents for both acute management of ACS and secondary prevention. Recent developments in oral antiplatelet therapy raised questions about the choice of the molecules, the use of single or double therapy, and the optimal dosing and duration of treatment. The present review aims to provide a current appraisal of antiplatelet therapy use after ACS and to summarize available scientific evidence for an optimal use of antiplatelet agents in daily practice, including the new P2Y12 blockers.