Five-year outcomes after coronary stenting are determined by restenosis of the original stented lesion during the first year and, later, by disease progression at non-stented segments, owing to either gradual progression of atherosclerosis or instability of vulnerable plaques. Drug-eluting stents have demonstrated potent anti-restenosis benefits in a variety of lesion types and high-risk patients, including complex long lesions and diabetic patients. It is likely that this benefit will translate into improved 5-year outcomes, with reduction in need for repeat revascularization in many patients and possibly reduced incidence of myocardial infarction and death, especially in diabetic patients, in whom the risk for occlusive restenosis and 5-year death and myocardial infarction rates are known to be higher after bare-metal stents. Future studies will determine the role of drug-eluting stents in preventing adverse outcomes owing to later disease progression. Such strategies and proposed clinical trials may include identification and prophylactic stenting of individual vulnerable plaques or coronary segments, and comparisons with coronary artery bypass surgery for complete revascularization success. While the outlook for benefit of drug-eluting stents in 5-year outcomes is hopeful, it is likely that a true improvement in these outcomes will be realized more from a judicious use of drug-eluting stents coupled with other proven aggressive secondary prevention therapies.