Stent restenosis, especially the diffuse pattern, has developed into a significant clinical and economical problem. It has been estimated that up to 250,000 patients developed in‐stent restenosis in 2,000 alone, two thirds of them can be expected to have diffuse in‐stent restenosis, which is difficult to treat because of high recurrence rates. None of the conventionally available interventional treatment modalities provides optimal long‐term results. Intravascular radiation therapy is currently the only effective percutaneous therapy, for combating in‐stent restenosis. Late thrombotic complications have largely been eliminated by extended antiplatelet regimens. Geographical miss, a major reason for recurrence of in‐stent restenosis after brachytherapy, can be reduced by an improved radiation technique. The first preliminary data on drug‐eluting stents, showing only minimal neointimal proliferation at 6‐month postimplantation, could represent a major breakthrough in the quest to solve restenosis.