In patients with an acute coronary syndrome (ACS), inhibition of the platelet P2Y12 receptor is standard of care. The shortcomings of the most commonly used P2Y12 receptor inhibitor clopidogrel-that is its delayed onset of action, its interindividual response variability, and the phenomenon of high on-treatment platelet reactivity-led to the development of more potent P2Y12 receptor inhibitors (prasugrel and ticagrelor) that proved their superiority in terms of reducing thrombotic events compared to clopidogrel. Available randomized studies that aimed at investigating the value of a personalized antiplatelet treatment regimen based on platelet function monitoring results were negative with regard to the possible benefits of monitoring but were all limited by mainly enrolling elective and stable patients with coronary artery disease. Thus, it still warrants further investigation if a tailored, platelet function guided, antiplatelet therapy in ACS patients with the available P2Y12 receptor inhibitors prasugrel, ticagrelor, and clopidogrel can lead to improved patients outcome.