Many patients suffer thrombotic events such as myocardial infarction, stroke and peripheral embolism despite therapy with recommended doses of all currently approved antiplatelet agents. Researchers have suggested that a subset of patients may be resistant to the antiplatelet effects of aspirin, and have developed substantial evidence to support this theory. The thienopyridines ticlopidine and clopidogrel and the glycoprotein IIb/IIIa inhibitors also exhibit substantial interpatient variability in the level of platelet inhibition they achieve. There are several biochemical factors that may contribute to the etiology of individual resistance to antiplatelet medications. Some studies suggest that the variability in patient responsiveness to these drugs may have clinical consequences, and data from trials evaluating clinical end points are needed to further elucidate this correlation.