In the last decade, several studies reported a high inter-individual variability in the pharmacological response to antiplatelet drugs. Suboptimal response to aspirin, as determined by specific tests (serum thromboxane B(2)), is rare and, when present, it appears to be caused by poor compliance in most instances. In contrast, studies that used specific tests to measure the pharmacological effect of clopidogrel showed a wide variability of response, with about 1/3 of treated subjects who are very poor responders. Inter-individual difference in the extent of metabolism of clopidogrel to its active metabolite by cytochrome P450 isoforms is the most relevant cause of the observed inter-individual variability in platelet inhibition. Tailored treatment based on laboratory monitoring of platelet function has been proposed as a solution to poor responsiveness to clopidogrel. However, we still need to identify the ideal laboratory test and to answer basic questions on its clinical utility and cost-effectiveness, before monitoring clopidogrel therapy can be recommended in clinical practice.