Hepatic cytochrome P450 (CYP) bioactivation of clopidogrel is reduced in subjects with the CYP2C19*2 loss-of-function allele. This allele has been linked to an increased risk of stent thrombosis after percutaneous coronary intervention. In contrast to clopidogrel, the effect of newer antiplatelet agents, e.g., prasugrel and ticagrelor, is not dependent on CYP2C19. This review briefly outlines the current evidence for the value of CYP2C19 genotyping to guide antiplatelet therapy with clopidogrel. Prospective trials of new treatment algorithms are awaited before routine adoption of CYP2C19 genotyping for this purpose.