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 cardiovascular disease has been evaluated in large-scale randomised trials, however the absolute benefit for an individual patient and a specific platelet-active drug needs further evaluation. Several well-conducted studies have demonstrated a substantial inter-individual variability in platelet responsiveness to drugs. The historical "gold standard" test of platelet function (optical aggregation) has been extensively used for measuring the effect of antiplatelet drugs, but has limitations. 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 of a consensus regarding the definition of resistance and the relevant test, (ii) the demonstration that biological resistance has clinical significance, and (iii) the clinical impact of individually adjusting 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.