Coronary stenting is currently the dominant and most cost-effective interventional approach in managing symptomatic artery diseases. Stent restenosis is the phenomenon of arterial vessel re-narrowing following an angioplasty procedure and is the most common complication of the stenting procedure. Drug-eluting stents (DES) nearly eliminate stent restenosis in simple lesions and significantly reduce its incidence in complex lesions. This chapter provides an overview of the pathophysiology of restenosis and the various considerations that go into the design and development of a successful DES including stent platform and materials, drug carriers, selections of various classes of anti-restenotic agents, and the appropriate modulation of drug load and release duration. Detailed examinations of the leading marketed drug-eluting stents are provided, followed by a brief introduction to devices that are in the development stage which may become the next-generation DES.