Local delivery of immunosuppressive or antiproliferative agents using a drug-eluting stent is a new technology that is supposed to inhibit in-stent restenosis, thus providing a biological and mechanical solution. This technique is a very promising. To date, several agents have been used, including paclitaxel, QP-2, rapamycin, actinomycin D, dexamethason, tacrolimus, and everolimus. Several studies, published recently or still ongoing, have evaluated these drugs as to their release kinetics, effective dosage, safety in clinical practice, and benefit. These studies include: SCORE (paclitaxel derivative), TAXUS I-VI, ELUTES, ASPECT, DELIVER (paclitaxel), RAVEL, SIRIUS (sirolimus), ACTION (actinomycin), EVIDENT, PRESENT (tacrolimus), EMPEROR (dexamethason), and FUTURE (everolimus). Paclitaxel was one of the first stent-based antiproliferative agents under clinical investigation that provided profound inhibition of neointimal thickening depending on delivery duration and drug dosage. The randomized, multicenter SCORE trail (Quanam stent, paclitaxel-coated) enrolled 266 patients at 17 sites. At 6-month's follow-up, a drop of 83% in stent restenosis using the drug-eluting stent could be achieved (6.4% drug-eluting stent vs 36.9% control group), which was attributable to a remarkable decrease in intimal proliferation. Unfortunately, due to frequent stent thrombosis and side-branch occlusions, the reported 30-day MACE rate was 10.2%. The randomized TAXUS-I safety trial (BSC, NIRx, paclitaxel-coated) also demonstrated beneficial reduction of restenotic lesions at 6-month's follow-up (0% vs 10%) but was associated with the absence of thrombotic events presumably due to less drug dosage. The ongoing TAXUS II-VI trials are addressing additional insight regarding the efficacy of the TAXUS paclitaxel-eluting stent. ASPECT and ELUTES evaluated paclitaxel-coated stents (i.e., Cook and Supra G), including subgroups with different drug dosages. With respect to stent restenosis and neointimal proliferation, both studies demonstrated a clear dose response. The RAVEL and the SIRIUS trials evaluated sirolimus-coated stents (i.e., Cordis, Johnson & Johnson, and Bx VELOCITY stents). Results confirmed the beneficial findings regarding reduction of renarrowing using a drug-eluting stent without any major adverse effects. Although parameters such as drug toxicity, optimal drug dosage, or delayed endothelial healing still need to be evaluated, today's clinical experience indicates that drug-coated stents are extremely beneficial in the interventional treatment of coronary lesions.