Platelets play an important role in the pathogenesis and the ischemic complications ofatherosclerosis. Platelets may be activated by several different agonists, promoting therelease of their granule contents and subsequent aggregation and thrombus formation; thisleads to ischemic events such as myocardial infarction or stroke. Aspirin, the most popularantiplatelet agent, is a cornerstone in the treatment and prevention of ischemic events incardiovascular patients. It inhibits a particular amplification pathway of platelet activation,based on thromboxane A2 (TxA2) generation. However, despite a consistent inhibition ofTxA2 production, a substantial proportion of patients display preserved platelet function.This phenotype is defined as “high on-treatment platelet reactivity”. It is a risk factor forthe recurrence of ischemic events, particularly in acute vessel injury settings. The determi-nants of platelet reactivity in these patients remain unclear, but previous studies, includinghealthy subjects, suggested that it is genetically determined.