The decrease in restenosis rates compared with conventional angioplasty, stable angiographic results with a subsequent decreased need for urgent or emergency coronary bypass graft surgery, and reliable treatment of acute or threatened closure resulting from conventional angioplasty have all made stents the treatment of choice for many patients undergoing percutaneous intervention. In-stent restenosis (ISR), however, has become a significant problem. Neointimal hyperplasia with vascular smooth muscle cells is even more exaggerated with stent placement than with conventional angioplasty. In addition, failure to deploy the stent optimally at the time of the initial placement may result in increased restenosis. Symptoms of ISR typically occur within 6 to 9 months following intervention, and range from asymptomatic angiographic narrowing, or even occlusion, to recurrent angina/ischemia or myocardial infarction. Evaluation is by repeat angiography. Treatment with balloon angioplasty is effective for focal in-stent restenotic lesions; for other lesions excimer laser, rotational atherectomy, and directional coronary atherectomy are associated with excellent initial outcome, but long-term outcome of these procedures is unclear. Brachytherapy with both gamma and beta sources has been found to result in improved outcome with less angiographic restenosis and decreased target vessel revascularization. Late thrombosis has been documented in up to 10% of patients treated with vascular gamma brachytherapy, and increased stenosis at the edges of the treated segment is also seen. Prolonged dual antiplatelet therapy and avoidance of a new stent has been shown to reduce late thrombosis in patients treated with vascular brachytherapy.