Some patients with acute coronary syndromes and/or who are undergoing percutaneous coronary interventions (PCI) remain at risk for cardiovascular events despite antiplatelet treatment with clopidogrel. This may be due, at least in part, to high residual on-treatment platelet reactivity (PR). Given the potential seriousness of an incomplete response to treatment, there is a need for a simple, rapid and reproducible point-of-care method to determine the patient's response to clopidogrel in order to tailor treatment in routine clinical practice. Among the available assays to measure the degree of platelet inhibition, the VerifyNow P2Y12 system is a simple test based on agglutination of fibrinogen-coated beads. Numerous studies have used this system to assess on-clopidogrel PR in an attempt to define a reliable cut-off for identifying patients at risk for a cardiovascular event. Despite substantial evidence to support a role for PR testing in routine clinical practice to stratify the risk of cardiovascular events in patients who undergo PCI, definitive clinical evidence is still lacking for the utility using PR data to tailor clopidogrel treatment. Issues include the risk profile of patients enrolled in studies, the timing of assessment of PR and the fact that PR has been shown to change over time. Genetic susceptibility may explain some of the variability in PR, and genetic testing could provide additional information for clinical decision-making. Nevertheless, until new evidence from well designed clinical studies is available, the implementation of current treatment guidelines and the administration of newer, more potent oral P2Y12 receptor blockers remains the standard-of-care.