In-stent restenosis (ISR) caused by neointimal hyperplasia is the major drawback after percutaneous coronary intervention (PCI) for obstructive coronary disease, occurring in up to 40% of lesions. Recently, one of the most intriguing new therapies developed is drug-eluting stents (DES) that target the central phenomenon of cellular proliferation that causes ISR. The benefits of stent-based drug delivery include maximizing the local tissue levels of therapeutic agents while minimizing systemic toxicity. Numerous DES using different thin-film polymeric drug carrier have been developed and tested, those eluting either antimitotic or antimicrotublar agents such as sirolimus and paclitaxel have been shown effective in clinical trials. Two DES, the J Cypher (sirolimus-eluting) and the Boston Scientific Taxus (paclitaxel-eluting) stents, are commercially available in the U.S. after a number of randomized trials demonstrated reductions in late lumen loss, binary restenosis rate, and need for repeat revascularization compared with bare-metal stents (BMS). Because ISR is multifactorial, ideal agents for DES should inhibit thrombus formation, inflammation and cellular proliferation as well as enhance re-endothelialization. The next generation of DES currently undergoing preclinical studies includes new technology, new stent designs and materials, biological polymers, bioabsorbable stents coated with new drugs including stent based gene, as well as cell delivery. The current paper will review and discuss the current and future status of DES.