Percutaneous transluminal coronary angioplasty revolutionized therapy for coronary artery disease. This early promise of a viable alternative to surgical treatment of coronary artery disease was thwarted by the high rates of angiographic restenosis. The advent of stenting reduced the rates of restenosis, although it was hindered by the new problem of in-stent restenosis. It was demonstrated that in-stent restenosis was the result of a new pathology in the form of neointimal hyperplasia, which was a maladaptive healing response to bare-metal stent implantation. Recently, the introduction of drug-eluting stents (DES) technology has offered a new solution to the problem of restenosis. Current evidence suggests that although DES have reduced restenosis rates, important concerns have been raised regarding increased stent thrombosis, myocardial infarction and death. The purpose of this article is to examine the efficacy and safety data of DES as highlighted in recent publications and to further discuss the biomolecular mechanisms of accelerated endothelization and stent thrombosis. In addition, we will examine some of the newer stent technologies available.