Despite recent pharmacologic and mechanical innovations that have improved acute procedural outcomes, restenosis remains a major limitation of all percutaneous revascularization techniques. Early models of restenosis implicated excessive proliferation and secretion by smooth muscle cells as the primary process responsible for luminal renarrowing after angioplasty. However, the failure of a multitude of pharmacologic agents aimed at inhibiting neointimal hyperplasia to limit restenosis in clinical trials coupled with recent experimental observations has served to highlight the importance of other mechanisms involved in stenosis recurrence. Intracoronary stents, which essentially eliminate immediate elastic recoil and late vascular remodeling following angioplasty, have demonstrated the ability to reduce both angiographic and clinical parameters of restenosis in selected patients. Likewise, potent antiplatelet therapy with the chimeric platelet glycoprotein IIb/IIIa receptor Fab has recently been shown to improve late clinical outcome following angioplasty in two large randomized trials. Several emerging therapeutic approaches targeting restenosis, including locally delivered radiation, gene-based therapy, and a variety of novel pharmacologic agents, have shown promise in preclinical and preliminary clinical studies...