Percutaneous coronary intervention is widely used to reduce the risk of death or cardiovascular events in patients with acute coronary syndromes. Dual antiplatelet treatment with aspirin and clopidogrel has become routine practice to prevent thrombotic events after coronary surgery. Despite advances of significant reduction of thrombotic complications in this adjunctive therapy, major adverse cardiovascular events still occur, suggesting the need for development of novel antiplatelet agents that act as superior alternatives to current standard regimen. Recently developed antiplatelet agents (prasugrel, ticagrelor, cangrelor and elinogrel) efficiently antagonize P2Y12 receptor, a key platelet activating signaling pathway, and thereby inhibit aggregation induced by mediators such as ADP, collagen, thrombin and TXA2. We provide an evidence-based review on the pharmacological and clinical performance of clopidogrel and novel antiplatelet agents that antagonize P2Y12 receptors.