Drug-eluting stents, most commonly sirolimus-eluting stents and polymer-based paclitaxel-eluting stents, are now widely used during percutaneous coronary interventions, and have largely replaced bare-metal stents to treat a variety of native coronary artery and saphenous vein graft lesions. Stent thrombosis, a complication of both bare-metal and drug-eluting stents, is associated with significant morbidity and mortality including high rates of myocardial infarction and death. Recently, several studies in the literature have raised concern about increased rates of overall stent thrombosis and late stent thrombosis in drug-eluting stents in the so-called 'real world' where off-label uses of drug-eluting stents are common. Hypersensitivity reactions to the polymers used in drug-eluting stents, delayed endothelialization of the stents, and discontinuation of dual antiplatelet therapy have all been implicated in the pathophysiology of drug-eluting stents stent thrombosis. The incidence of total stent thrombosis as well as late stent thrombosis, however, does not seem to be significantly higher in drug-eluting stents than in bare-metal stents. An important risk factor for stent thrombosis in both types of stents appears to be the premature discontinuation of dual antiplatelet therapy, and physicians should educate their patients about the importance of adhering to dual antiplatelet therapy, given the dire clinical consequences of stent thrombosis.