When added to aspirin, clopidogrel at a routine dose of 75 mg daily reduces the incidence of thrombotic vascular adverse events in patients with acute coronary syndromes and those undergoing percutaneous interventions (PCI). The observation that many patients have less than expected platelet inhibition with clopidogrel has given rise to the concept of clopidogrel resistance. Clopidogrel resistance is associated with increased adverse events such as stent thrombosis, post-stent ischemic events and periprocedural myocardial infarctions. Some patients can overcome the resistance with increasing the dose of clopidogrel. A higher maintenance dose (150 mg daily) in patients undergoing PCI results in superior platelet inhibition and may reduce cardiovascular events. Clopidogrel is a thienopyridine prodrug, which is converted to its active metabolite by several enzymes of the P450 family, including CYP2C19. The loss-of-function CYP2C19*2 (681 G>A) single nucleotide polymorphism (SNP), occurring as either a hetero- or homozygous allele, reduces the conversion of clopidogrel to its active metabolite. Two recent studies have shown an association between CYP2C19*2 polymorphism and lack of platelet inhibition with clopidogrel. These studies included healthy volunteers and patients undergoing elective PCI and demonstrated a prevalence of the CYP2C19*2 allele of 25-30%. Platelet inhibition was not affected by clopidogrel in those who carried the CYP2C19*2 polymorphism.