In-stent restenosis (ISR) remains an important limitation after stent implantation occurring in 20-30% of patients. Different techniques and treatments have been evaluated in this setting. Repeat balloon angioplasty alone has been rapidly followed by ablative techniques such as laser, rotational atherectomy or implantation of a second stent within the stent. Cutting balloon represents another alternative technique. None of these techniques has proven its superiority over plain balloon angioplasty alone. Brachytherapy is the only effective treatment for ISR by significantly decreasing recurrent restenosis rate at follow-up. However, its use is limited by cost and infrastructure associated with the risk of late thrombosis requiring prolonged antiplatelet therapy. Surgical treatment can be proposed in recurrent ISR as well as medical therapy alone in pauci-symptomatic patients. New drug-eluting stents are under evaluation in this indication.