Several meta-analyses have demonstrated the superiority of drug-eluting stents (DES) in reducing the incidence of restenosis, target vessel revascularization and target lesion revascularization compared to their predecessor, the bare-metal stent. In comparing Cypher and Taxus stents, the two most recent meta-analyses have given the edge to the Cypher. However, it must be stressed that the superiority of one DES over another remains debatable due to ever changing "real-world data" compared to those attained from randomized trials. The newer sirolimus analogs and selective inhibitors are challenging the old guard in their quest to further limit restenosis. So too are the newer "high-tech" polymers and additionally by using more biodegradable material in the stent's design. Stents aimed at targeting lesions are a new armament in the battle against restenosis and together with combination therapies are exciting key areas to watch. The ideal way to treat a DES in-stent restenosis is still a challenge and hence the impetus is to avoid it from happening in the first place.