The problem of restenosis after coronary angioplasty remains a major limiting factor of the procedure. Intracoronary stenting has led to a modest reduction in the frequency of this event. In the early 1990s, the effectiveness of ionizing radiation combined with balloon angioplasty and stenting was first convincingly demonstrated in animal models of restenosis. Small feasibility studies and two randomized trials have, in general, supported the promise of these initial preclinical studies in the prevention of restenosis. Much remains to be learned about the application of radiation for this therapy. This article reviews the current status of preclinical and clinical investigation of this therapy.