Resistance to the antiplatelet effects of both aspirin and clopidogrel is common and is associated with poorer clinical outcomes in patients receiving antiplatelet therapy. Available data indicate that hyporesponsiveness to clopidogrel is overcome in some patients by increasing the loading dose from 300 mg to 600 mg, with the higher loading dose being associated with reduced risk for adverse cardiovascular outcomes. Recent studies in patients undergoing coronary stent implantation indicate that antiplatelet resistance is associated with increased risk of stent thrombosis. A study in 804 patients receiving drug-eluting stents showed that nonresponse (defined as >70% aggregation at 10 micromol/L adenosine diphosphate) after a clopidogrel 600-mg loading dose was associated with a significantly increased risk of stent thrombosis (8.6% vs 2.3% for nonresponders vs responders, respectively) and cardiovascular death at 6 months. Another study in 380 patients showed that high posttreatment platelet reactivity (top tertile of values) on a rapid assay was associated with significantly greater out-of-hospital 6-month rates of stent thrombosis (4.0% vs 0.4% for high posttreatment reactivity group vs low posttreatment reactivity group, respectively), cardiovascular death, and nonfatal myocardial infarction. Further studies are needed to provide standardized definitions of antiplatelet resistance to better correlate resistance with clinical outcomes in patients receiving stents and to identify treatment alternatives in patients with resistance.