Dual oral antiplatelet therapy with aspirin and clopidogrel is the therapy of choice in patients with acute coronary syndromes and in patients undergoing coronary stent placement to lower the risk of thrombotic events. Responsiveness to aspirin and especially to clopidogrel is not uniform and is subject to considerable interindividual variability. Furthermore, there is a broad consensus that clopidogrel low response or so-called high on-treatment platelet reactivity is linked to the occurrence of ischemic events. On the other hand, evidence is accumulating that enhanced clopidogrel responders are at increased risk of bleeding. Newer antiplatelet drugs, such as prasugrel and ticagrelor, are more potent and produce more consistent inhibition of platelet aggregation via the P2Y(12) ADP platelet receptor. A variety of methods of platelet function testing are available for evaluating platelet inhibition in percutaneous coronary intervention-treated patients in order to help determine the individual risk for ischemic and bleeding complications. Although not yet routinely undertaken, platelet function testing offers the potential to tailor antiplatelet therapy for individual patients. Whether alteration of therapy based on platelet function testing improves patients' outcomes remains unclear and is currently under investigation. This article reviews the impact of antiplatelet drug responsiveness on clinical outcomes with a focus on P2Y(12) receptor inhibition as well as on current and future concepts for personalized antiplatelet strategies.