The introduction of drug-eluting stents (DES) has rapidly and profoundly affected the field of interventional cardiology, and DESs are now used in a majority of intracoronary stenting procedures. As a result of the innumerable "trial-and-error" endeavors, DESs have emerged as a potential solution for solving the problem of restenosis. DESs are coated stents capable of releasing single or multiple bioactive agents into the bloodstream and the surrounding tissues. The efficacy and safety of DESs might differ depending on the pharmacologic agents and stent delivery systems that are used. Recent research has focused on the various constituents of DESs, including the stent backbone, the materials used as drug-delivery vehicles, and the physicochemical properties of the pharmacotherapeutic agents themselves. Stent-induced mechanical arterial injury and a foreign body response to the prosthesis incite acute and chronic inflammation in the vessel wall, along with the elaboration of cytokines and growth factors that induce multiple signaling pathways to activate smooth muscle cell migration and proliferation. Utilization of antiproliferative agents delivered locally via the drug-eluting stents has dramatically reduced the stent restenosis rate. The polymer-regulated delivery of both paclitaxel and sirolimus at the site of arterial injury has been shown to reduce the clinical and angiographic restenosis rates after stent implantation in de novo coronary lesion. Other DESs have yielded somewhat less brilliant results or even true failures, while a number of new drugs and new stent platforms are now under clinical or preclinical evaluation. In this review, we describe the main clinical trials on DESs and the most recent information that has been derived from observational studies and registries. Moreover, the preliminary results on the new DESs are also summarized.