Antiplatelet therapy is used to reduce the risk of ischemic events in patients with cardiovascular disease. The balance of benefits and risks of antiplatelet drugs in coronary artery disease has been evaluated in large-scale randomised trials, however the absolute benefit for an individual patient and a specific platelet-active drug need further evaluation. Several well-conducted studies have demonstrated a substantial inter-individual variability in the platelet responsiveness to drugs. The historical “gold standard” test of platelet function (optical aggregation) has well established limitations for measuring the effect of antiplatelet drugs. Other new tests developed (i.e. PFA-100®, VerifyNow®) may overcome some of these limitations but they do not correlate well with each other. Despite these unresolved methodological questions, several recent clinical studies, but not all, suggest a significant correlation between antiplatelet resistance status and serious vascular events. In these conditions, laboratory monitoring for antiplatelet therapies raises several questions: (i) the necessity for a consensus on the definition of resistance and on the best test for evaluation of the condition, (ii) the demonstration that biological resistance has clinical significance, and (iii) the clinical impact of adapting the antiplatelet therapy. Therefore, it is not currently appropriate to test patients or to change therapy on the basis of such tests, other than in prospective and adequately powered clinical trials.