Saphenous vein graft (SVG) disease has been an obstinate problem facing the cardiologist since the early days of coronary artery bypass grafting (CABG) surgery. SVG disease follows temporally distinct phases of thrombosis, intimal hyperplasia and progressive atherosclerosis leading to recurrent ischemia which can be treated with repeat operation or percutaneous revascularization. However, repeat operation is associated with high mortality and morbidity. Also, percutaneous treatment of SVG disease is complicated by a high rate of procedural and long term complications due to the interrelated phenomena of distal embolization, slow flow or no reflow, periprocedure myocardial infarction, and subsequent restenosis. Long-term patency is poor in this patient population regardless of the treatment modality. Many pharmaceutical and device based approaches have been tested to avert these complications, but few, such as the use of distal protection devices, have shown benefit. The novel drug-eluting stents show promise in reducing the occurrence of restenosis and solving one of the problems associated with the percutaneous treatment of SVG disease. The pathogenesis and therapeutic options for SVG disease is reviewed in this article.