Post-angioplasty restenosis is a major limitation of interventional cardiology. A large body of evidence reveals that expression of myofibroblast activity promoters moves progressively from the neoadventitia to the neointima. Brachytherapy inhibits vascular cell activity (proliferation, migration), mitigates recruitment of intimal cells, and shows a favorable prophylactic effect on late vascular remodeling by preventing adventitial constriction at the injured site. These effects of brachytherapy are dose related. Clinical and experimental data demonstrate that restenosis is determined by the balance between arterial remodeling and intimal hyperplasia. Apparently, brachytherapy-induced positive remodeling plays the principal role in increasing the luminal diameter after PTCA and, in case of a lower dose or dose fall-off, to cause detrimental edge effects. With regard to clinical course, healing defects, endothelial dysfunction and stent-vessel wall malapposition are apparently important and possibly underestimated features of vascular pathology, since they may contribute to late thrombosis and delayed intimal hyperplasia in long-term course after intracoronary brachytherapy.