Local delivery of immunosuppressive or antiproliferative agents using a drug-eluting stent is a new technology meant to inhibit in-stent restenosis providing both a biological and mechanical solution and has recently emerged as a very promising approach. Up to now several agents have been in use: Paclitaxel, Rapamycin, Actinomycin D or Tacrolimus. Evaluating these drugs regarding their release kinetics, effective dosage, safety in clinical practice and benefit, several studies have been published or are still ongoing: SCORE (Paclitaxel-derivative), TAXUS I, II, III, IV (Paclitaxel), ELUTE, ASPECT (Paclitaxel), RAVEL, SIRIUS (Sirolimus), ACTION (Actinomycin), EVIDENT, PRESENT (Tacrolimus). Paclitaxel was the first stent-based antiproliferative agent under clinical investigation providing 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 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) attributable to a remarkable decrease in intimal proliferation. Unfortunately, due to both frequent stent thrombosis and side-branch occlusions the reported 30-day MACE rate was 10.2%. The randomized TAXUS I safety trail (NIRx, Paclitaxel coated) also demonstrated beneficial reduction of restenotic lesions at 6-month FU (0% vs. 11%) but, this time, associated with the absence of thrombotic events presumably due to the lower drug dosage. The ongoing TAXUS II, III and IV trails are aimed at providing additional insight regarding the efficacy of the TAXUS Paclitaxel-eluting stent. Both the RAVEL and the SIRIUS trial have been conducted to evaluate a Sirolimus-coated stent (Bx VELOCITY stent). From the results available, the beneficial findings regarding reduction of renarrowing using a drug-eluting stent have been confirmed without any adverse effects. Although parameters like drug toxicity, optimal drug dosage or delayed endothelial healing need to be further evaluated, summarizing the today's clinical experience the strategy of drug-coated stents promises a striking benefit in interventional treatment of coronary lesions.