Dual antiplatelet therapy (aspirin plus clopidogrel) is mandatory in patients treated with coronary stent implantation. This strategy is highly effective in prevention of stent thrombosis until its struts are covered with endothelium. However, a substantial number of patients still suffer from recurrent ischemic coronary events despite adequate antiplatelet therapy. These events fall into three categories: stent thrombosis, in stent restenosis and events related to other non-stented coronary lesions. Some data suggest that beside other local and systemic factors resistance to aspirin and clopidogrel may be a possible cause of stent thrombosis and ischemic events in patients after coronary interventions. Several mechanisms of antiplatelet drug resistance have been reported including poor compliance, interactions with other drugs, genetic polymorphism or increased platelet turnover. More research is needed to adequately assess the clinical significance and prognostic value of antiplatelet drug resistance detected by laboratory tests in patients undergoing percutaneous intervention. We review published data on mechanisms and the clinical significance of aspirin and clopidogrel resistance in patients after coronary interventions.