Intracoronary radiation therapy for prevention of restenosis is a new emerging technology which is tested nowadays in clinical trials. Several methods of radiation and a variety of isotopes have been tested in different animal models in order to prove the concept and to find a friendly user system for this application. Using the same treatment doses both gamma and beta emitters demonstrated similar results despite differences in isotope characteristics: penetration, activity, dose rate and treatment time. In addition, intracoronary radiation delivered via a catheter-based system prior to coronary stenting showed reduction of neointimal hyperplasia in the porcine coronary stent model and may further reduce restenosis coupled to stent implantation. The value of radioactive stents is also considered especially in large vessels with regard to their low activity and their proximity to the vessel wall. Adventitial labeling and immunostaining suggested the mechanism by which radiation reduces smooth muscle cell proliferation at the adventitia and affects on favorable vessel remodeling. These studies which were pioneered in this new field and have facilitated the clinical trials of using radiotherapy for prevention of restenosis are reviewed and discussed in this paper.