Restenosis is the limiting entity following coronary angioplasty. It is associated with significant morbidity, mortality and cost, and thus represents a major clinical and economical problem. Despite technical improvements, restenosis after conventional balloon angioplasty occurs in 30 - 60% of cases. Coronary stenting was able to reduce the incidence by approximately 30%; nevertheless, some 250,000 patients experience in-stent restenotic lesions/year worldwide. In-stent restenosis has been recognised as very difficult to manage, with a repeat restenosis rate of 50%, regardless of the angioplasty device used. So far, only vascular brachytherapy has convincingly reduced the incidence of repeat in-stent restenosis (by 50%) and thus, has emerged as the gold standard of therapy. The introduction of drug-eluting stents has shown a great deal of promise for the treatment of both de novo and restenotic lesions, with reported restenosis rates of < 10%, and benefit for virtually all patient subsets at a higher risk of restenosis. This review outlines the pathophysiology, epidemiology and predictors of the restenosis process, and places emphasis on the various treatment options for its prevention and therapy.