In-stent restenosis is an increasing problem due to the frequent use of coronary stent as a form of percutaneous revascularization. The global incidence is near to 28%, and it is well document that a neointimal hyperplasia is its principal mechanism. The most commonly related factors for its appearance are diabetes mellitus, a longer length of the original lesion, a smaller diameter of the reference vessel, the left anterior descending artery location and a smaller luminal diameter at the end of the procedure. Due to a different long term evolution in-stent restenosis has been classified as focal or diffuse, according to the length of the restenotic lesion (focal < 10 mm and diffuse > or = 10 mm). Some strategies have been proven for its treatment, but no randomized-controlled trials have been published comparing these different treatments. In focal in-stent restenosis the practice of a conventional balloon angioplasty is associated with high initial clinical success with a favourable long term evolution (target lesion revascularization between 11-15%). But on the contrary, in diffuse in-stent restenosis, in spite of a high initial success rate, an elevated target lesion revascularization has been detected at the follow-up (up to 43%). Other proved such as atherectomy or excimer laser are associated with a significant procedural non-Q-wave infarction (near to 9%) and a long term target lesion revascularization during follow-up (23-31%). The implantation of an additional stent has been performed with low procedural complications and with a long term target lesion revascularization near to 27%. Patients treated with intracoronary radiation as a complementary technique seem to have a better long term evolution than those having had the other strategies alone. In conclusion, in-stent-restenosis is a new and progressively more frequent problem, requiring complex treatment and of which as been established. Comparative controlled studies need to be performed in order to determine the best treatment for this new entity.