Data from a number of observational studies have dem- onstrated an association between an increased risk of adverse cardiovascular events and the presence of 1 of the nonfunc- tioning alleles17,18,20,21,23 27 and are well delineated in the ACCF/AHA Clopidogrel Clinical Alert.20 Prasugrel, the second FDA-approved P2Y12 receptor in- hibitor for use in ACS, is also a prodrug that requires conversion to its active metabolite. Prasugrel requires a single CYP-dependent step for its oxidation to the active metabolite, and at least 2 observational studies have demonstrated no significant decrease in plasma concentrations or platelet inhibition activity in carriers of at least 1 loss-of-function allele of the CYP2C19 isoenzyme.28,29 On the other hand, ticagrelor, the latest FDA-approved P2Y12 receptor inhibitor, is a nonthienopyridine, reversible, direct-acting oral antago- nist of the P2Y12 receptor that does not require transformation to an active metabolite.30 Since the FDA announced a Boxed Warning on March 12, 2010, about the diminished effectiveness of clopidogrel in patients with an impaired ability to convert the drug into its active form,14 there has been much interest in whether clinicians should perform routine testing in patients being treated with clopidogrel. The routine testing could be for genetic variants of the CYP2C19 allele and/or for overall effective- ness for inhibition of platelet activity. The ACCF/AHA Clopidogrel Clinical Alert expertly summarizes the issues surrounding clopi- dogrel and the use of genotype testing, as well as the potential for routine platelet function testing.20 The FDA label revision does not mandate testing for CYP2C19 genotypes or overall platelet function.14 The revi- sion serves to warn clinicians that certain patient subgroups may exhibit reduced clopidogrel-mediated platelet inhibi- tion and emphasizes that clinicians should be aware of alternative treatment strategies to tailor alternative thera- pies when appropriate. 