Treatment failures occur with any drug and aspirin is no exception. Evidence is growing to indicate that there are subpopulations that do not respond to antithrombotic action of aspirin. The term 'aspirin resistance' has been used to describe a number of different phenomena, including inability of aspirin to: (i) protect against cardiovascular events despite its regular intake; (ii) to affect various laboratory tests, reflecting platelet activity. Research on aspirin resistance yielded interesting results in clinical pharmacology and pharmacogenetics. Future studies will show whether genotyping for polymorphisms might be of value in everyday clinical use of aspirin. Present data indicate that in survivors of recent myocardial infarction or unstable angina, patients receiving coronary artery bypass grafts, as well as in subjects with hypercholesterolemia, aspirin resistance has to be considered when implementing antithrombotic therapy. However, in individual patients the available laboratory tests are of no particular use to predict reliably the clinical outcome or to guide in making therapeutic decision. Prospective clinical trials seem necessary to reach such conclusions.