Dual antiplatelet therapy with aspirin and a thienopyridine has become the standard of care for patients undergoing percutaneous intervention with stenting, regardless of indication. This article will examine the evidence for and against the use of aspirin and thienopyridines, with emphasis on platelet resistance and nonresponsiveness. Data suggest that in some patients, clopidogrel plus aspirin is not superior to aspirin alone. Resistance to aspirin and clopidogrel has been reported. Patients exhibiting aspirin resistance, as measured by an elevated platelet aggregate ratio, have a 10-fold increase in the risk of recurrent vascular events as compared to aspirin-sensitive patients. Clopidogrel nonresponsiveness has been a consistently observed phenomenon in studies utilizing various P2Y12 receptor-specific assays. Nonresponsiveness to clopidogrel treatment has been suggested as a risk factor for the occurrence of ischemic events and stent thrombosis.