Endovascular radiation therapy has proved to be safe and effective in preventing restenosis after coronary intervention both in animal studies and in pilot feasibility studies in humans. The rationale for such therapy is that radiation prevents neointimal proliferation and vessel constriction after vascular injury. Two forms of endovascular radiation therapy are available: catheter-based systems and radioactive stenting. However, several practical issues related to this technique still need to be addressed, such as questions about dosimetry, shielding, expense, handling and disposal of radioisotopes, certification for potential users, and-above all-safety and efficacy. In their pivotal studies, investigators and industry need to focus on prioritizing the clinical applications of this form of treatment. The clinical trials must attempt to determine the cost-effectiveness of this therapy as well as its risk versus benefit. For example, brachytherapy may prove to be of great benefit to patients with in-stent restenosis, and favorable results of studies examining this application should expedite the approval of endovascular radiation therapy for clinical use.