Over the past 15 years, despite a great deal of effort in assessing a variety of approaches, restenosis reduction has remained the most problematic complication of percutaneous transluminal coronary angioplasty (PTCA). Initial attempts focused on assessing systemic drugs including anticoagulant and antiplatelet agents, calcium antagonists and lipid-lowering agents. Subsequently, agents that were shown to significantly reduce neointima formation in animal models, including angiotensin-converting enzyme inhibitors, low molecular weight heparin, HMG-CoA reductase inhibitors, ketanserin and angiopeptin, were tested but were not found to be successful in restenosis reduction in clinical trials. The introduction of interventional techniques such as directional atherectomy rotational atherectomy and laser angioplasty on their own or as part of facilitated angioplasty or transcatheter device synergy have not generally reduced the frequency of restenosis. Stent implantation initially appeared promising with rates of around 20%–30% in so-called ‘ideal’ lesions, but with improvement of stent technology, the indications for stenting have broadened. Meanwhile the restenosis rate has remained significant with the rate ranging from 15%–50% at 6 months depending on the lesion morphology and other factors. In addition, the use of stents has led to the growing problem of in-stent restenosis. More recently, however, the concept and technique of applying ionizing radiation to the arterial wall during the percutaneous coronary intervention procedure has emerged and gained considerable momentum including entry into clinical trials.