Twenty-three years after introduction of coronary angioplasty (PTCA), the inhibition of restenosis formation continues to be the major challenge for the interventional cardiologist. About 35-50% of all patients undergoing PTCA develop a renarrowing of the intravascular lumen within the following six months. The use of specific systemic drug therapy as well as different angioplastic methods (rotablation, atherectomy, laser angioplasty) all failed to significantly reduce restenosis. Local drug delivery and local gene therapy have only shown to be effective in animal experiments. Restenosis can be reduced by the use of stents; however restenosis can also develop within the stents. The treatment of choice for severe in-stent restenosis may become radiotherapy, which seems to be a promising tool also for other forms of restenosis.