Antiplatelet therapy, targeting the inhibition of platelet function, ameliorates the survival of patients with clinically evident cardiovascular disease. The cornerstone of therapy is aspirin which was found to reduce of about 20% the relative risk of death, myocardial infarction and ischemic stroke. Clopidogrel in combination with aspirin is the recommended standard of care for reducing the occurrence of cardiovascular events in patients presenting with acute coronary syndromes undergoing percutaneous coronary intervention (PCI). Despite the benefits of current antiplatelet therapies, there are significant shortcomings, including hyporesponsiveness, delayed platelet inhibition, individual variability in response, a prolonged time to recovery. In addition, a growing body of evidence is demonstrating that a residual platelet reactivity on antiplatelets is associated with a significant increased risk of adverse clinical events. The optimal level of platelet inhibition to prevent cardiovascular events is modulated by clinical situation and at the moment we do not have a platelet function cut-off which is widely accepted to identify patients at high risk for ischemic events in the different clinical models. Ongoing clinical trials are evaluating if an antiplatelet treatment tailored on the entity of platelet inhibition will be a good strategy in terms of safety and efficacy. These studies will give us the crucial information on the possible utility of a monitoring of antiplatelets in order to prevent clinical events.