Aspirin is an effective antithrombotic agent for many patients. However, patients taking aspirin might exhibit variable responses to in vitro tests for platelet aggregation and might experience breakthrough thromboembolic events. Although this phenomenon has been called aspirin resistance, the lack of an uniform definition or agreement on diagnostic criteria precludes definitive recommendations at this time. Aspirin resistance has been defined in patients with cardiovascular, cerebrovascular, and peripheral vascular disease. In this article, mechanisms related with aspirin resistance and clinical background in which resistance is defined, are reviewed.