Aspirin is an effective antiplatelet agent with proven benefit in the prevention of atherothrombotic complications of cardiovascular disease. The antithrombotic effects of aspirin, however, are variable among individuals and this might explain, in part, why the absolute risk of recurrent vascular events in patients receiving aspirin therapy remains relatively high (8%–18% after 2 years). Although formal diagnostic criteria are lacking, aspirin resistance generally describes the failure of aspirin to produce an expected biological response or the failure of aspirin to prevent atherothrombotic events. Aspirin resistance has been reported to occur in 5% to 45% of the general population; therefore, its detection is potentially of clinical importance. The biological mechanisms, population prevalence, laboratory methods for detection, and clinical relevance of aspirin resistance are discussed in this review.