The introduction of coronary stents marked a major turning point in the practice of interventional cardiology. Whereas the efficacy of balloon angioplasty was challenged both by immediate mechanical complications and by a high incidence of restenosis, coronary stents offered cardiologists a means by which to not only augment immediate procedural success, but also to reduce the incidence of restenosis following coronary intervention. However, despite technological advances and an improved understanding of the restenotic process, the overall rate of in-stent restenosis following bare metal stent implantation remains high. Although the introduction of drug-eluting stents has further reduced the incidence of restenosis, the "real-world" application of drug-eluting stents in increasingly complex lesion and patient subsets has given way to the even greater clinical challenge of managing drug-eluting stent restenosis. Although the standard treatment of bare metal stent restenosis typically involves placement of a drug-eluting stent, the optimal therapeutic approach to drug-eluting stent restenosis remains less defined. The issue of in-stent restenosis (especially following implantation of a drug-eluting stent) remains a clinical challenge, and investigation into therapeutic options remains ongoing. As technology evolves, such investigation will likely incorporate novel approaches including drug-coated balloons novel stent designs.