Antiplatelet agents have long served as the cornerstone of pharmacologic therapy to prevent atherothrombotic events. The thienopyridines have risen to prominence as both an alternative and adjunctive treatment to aspirin monotherapy. These agents prevent platelet aggregation by selectively and irreversibly blocking the platelet ADP P2Y12 receptor. In this article we focus on the use of clopidogrel in the contemporary management of coronary artery disease. We assess the use of clopidogrel following revascularization for coronary artery disease with percutaneous coronary intervention, particularly after deployment of drug-eluting stents. Finally, we address some aspects of clopidogrel resistance.