Drug-eluting stents reduce the occurrence of in-stent restenosis and the need for subsequent target vessel revascularization compared with bare-metal stents. However, the safety of drug-eluting stents has been called into question because of an apparent increase in late stent thrombosis, a frequently fatal event. A substantial body of research has focused on determining the magnitude of these competing events, often reaching contradictory results even with analyses of the same data. Although larger, adequately powered, randomized trials are needed to fully assess the net clinical effects of drug-eluting stents compared with bare-metal stents, the evidence seems to suggest that the net clinical benefit of drug-eluting stents may outweigh their risks. The evidence is clearer that premature discontinuation of antiplatelet therapy is an important trigger for stent thrombosis; therefore, patients who are candidates for implantation of drug-eluting stents should be screened for their ability to receive and tolerate uninterrupted antiplatelet therapy longer than is necessary with bare-metal stents. The evidence suggests that drug-eluting stents relieve obstructive coronary artery disease, provide durable mechanical results, and do more good than harm, but all patients also should be given antiplatelet and other optimal medical therapies to achieve the best outcomes.