The P2Y12 receptor plays a critical role in the amplification of platelet aggregation in response to various agonists and stable thrombus generation at the site of vascular injury leading to deleterious ischemic complications. Therefore, treatment with a P2Y12 receptor blocker is a major effective strategy to prevent ischemic complications in high -risk patients with acute coronary syndrome (ACS) and patients undergoing percutaneous coronary intervention (PCI). The determination of optimal platelet inhibition is based on maximizing antithrombotic properties while minimizing bleeding risk and is critically dependent on individual patient's propensity for thrombotic and bleeding risks. Immediately after ACS during PCI, where highly elevated thrombotic activity is present, a loading dose administration with a potent P2Y12 receptor blocker such as ticagrelor or prasugrel is preferred. In stable coronary artery disease patients undergoing PCI, clopidogrel is widely used. In addition, in patients with ST-segment elevation myocardial infraction (MI) who cannot take oral medications, a fast acting intravenous glycoprotein IIb/IIIa inhibitor or P2Y12 receptor blocker, cangrelor, may add clinical benefits. During long term therapy, a strategy that prevents ischemic risk while avoiding excessive bleeding risk is similarly desired. Although up to one year dual antiplatelet therapy (DAPT) is recommended in patients undergoing elective stenting, the available data support the anti-ischemic benefit of prolonged DAPT (more than1 year) in patients with prior MI. In addition to the DAPT risk calculator tool, future risk assessment methods that analyze intrinsic thrombogenicity and atherosclerotic coronary burden may further identify the optimal candidate for prolonged DAPT to improve net clinical outcomes.