Aspirin is the cornerstone of treatment in patients with coronary artery disease. However, several studies investigating the in vitro response of platelets to the administration of aspirin showed this response to be variable, with some patients exhibiting non-responsiveness or resistance. Aspirin resistance may be categorised as either 'laboratory' or 'clinical'. Laboratory aspirin resistance is defined as the failure of aspirin to inhibit the production of thromboxane A(2) (TxA(2)) by platelets or to inhibit platelet activation that depends on TxA(2) production. Clinical aspirin resistance is defined as the failure to prevent the occurrence of atherothrombotic ischaemic episodes in patients to whom it is administered. So far, there is no generally accepted method for the ex vivo evaluation of platelet activation or for assessing the degree of platelet activation following aspirin administration and data concerning the clinical impact of aspirin resistance are conflicting. For these reasons it is not possible to suggest specific guidelines for the treatment of patients who show high levels of platelet activation or a low level of platelet inhibition after treatment with aspirin. The aim of this review is to present data from laboratory and clinical studies that are related to resistance to aspirin, and to discuss the possible causes, the clinical significance, and the ways of managing such resistance at a clinical level.