Prasugrel is a third-generation thienopyridine that inhibits ADP-induced platelet activation by irreversibly blocking the P2Y12 receptor. Given in healthy volunteers in dosages used clinically, it invariably inhibits platelet aggregation. When administered in patients, it has been shown to result in a faster, more consistent and stronger inhibition of platelet aggregation compared with the most widely used clopidogrel. However, cases of inadequate platelet inhibition or of the so-called ‘resistance’ to prasugrel have been occasionally reported. The focus of these reviews is prasugrel resistance prevalence, mechanisms and potential clinical implications.