Drug-eluting stents (DESs) have largely demonstrated their superiority to bare-metal stents (BMSs) with respect to in-stent restenosis. Since the US Food and Drug Administration (FDA) approved the first DES in 2003, there has been a significant increase in the use of these devices. They are used in 70-80% of all stent procedures worldwide. Nevertheless, safety concerns stemming from reports of increased risk of late stent thrombosis (ST) and myocardial infarction (MI) have tempered the enthusiasm that the advent of these stents originally generated. New generation DESs with novel polymers, antiproliferative drugs, and improved platforms are now approved and available for use. In this review we provide a critical appraisal, based on published clinical data, of the safety and efficacy of various DESs.