Numerous genetic variants have been studied in the context of antiplatelet responsiveness, particularly for aspirin and clopidogrel. The majority of these variants have failed to demonstrate any measurable level of clinical validity with the exception of the CYP2C19*2 allele. Several studies have identified a link between CYP2C19*2 carriers and decreased clopidogrel responsiveness as assessed by platelet reactivity testing and clinical outcomes. The FDA boxed warning and strong evidence of the CYP2C19*2 allele provide a compelling indication to alter treatment when genotype information is available. However, several questions remain and universal genotyping cannot be recommended at this time without further studies that establish the clinical utility of genomic testing for clopidogrel.