Aspirin is the most commonly used therapeutic agent in prevention of vascular ischemic events. Aspirin exerts its antithrombotic effect primarily by interfering with the biosynthesis of thromboxane A2 (TXA2) and inhibition of TXA2 -dependent platelet aggregation. A meta-analysis of secondary prevention trials indicated that aspirin reduced major cardiovascular or cerebral events by 25%. This led to the widespread use of aspirin for prevention of cardiovascular events. However, it appears that aspirin antiplatelet effect is not uniform in all patients and previous studies estimated that 8-45% of the population were aspirin resistant. Furthermore, (i) the optimal dosage of aspirin for complete inhibition of platelet aggregation by physiological agonists (i.e arachidonic acid) is subject to great interindividual variability, (ii) the tests to detect aspirin resistance in vitro are subject to debate and (iii) the mechanisms by which some patients are resistant to aspirin in vitro remain to be determined. Despite these unresolved questions, recent clinical studies provide the reliable evidence that aspirin resistance correlates with confirmed clinical unresponsiveness, highlighting the clinical interest of determining the aspirin inhibitory effects on patients' platelets. In conclusion, discovery of aspirin resistance in individuals might be important in order to devise better anti-platelet strategies and improve our ability to prevent acute thrombotic complication.