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Summary.  Aspirin, an irreversible inhibitor of platelet prostaglandin synthase activity, is the cornerstone of therapy for acute coronary syndromes. In recent years, laboratory and clinical data have accumulated that suggest there may be significant individual variability in the response to aspirin and that the effects of aspirin therapy vary significantly over time. There is, as of yet, no cohesive explanation for this variability. The term ‘aspirin resistance’ has been loosely applied to situations in which the clinical or ex vivo effects of aspirin are less than expected. In this review we discuss the clinical data regarding this phenomenon and the need for prospective evaluation of aspirin non-responders.