Intracoronary stents reduce restenosis compared with balloon angioplasty. However, a major limitation of stenting is in-stent restenosis, which occurs in 10% to 40% of the patients depending upon risk factors. Serial intravascular ultrasound studies have shown that in-stent restenosis is primarily due to neointimal hyperplasia. Treatment of in-stent restenosis is challenging and recurrence rates are high regardless of interventional technique used. Several randomized clinical trials with intracoronary ionizing radiation using both beta (b) and gamma (g) emitters following primary catheter-based intervention have demonstrated a significant reduction in recurrence. The majority of these studies have used both serial angiographic and serial intravascular ultrasound endpoints to assess the efficacy of intracoronary radiation to prevent recurrence after the treatment of in-stent restenosis. As different mechanism of postradiation restenosis may operate in the original lesion segment, the ballooned segment and the actual irradiated segment, these imaging techniques have also helped to document any long-term affects of radiation including aneurysm formation, edge effects, geographical miss, and the presence or absence of remodeling. The angiographic results have correlated well with intravascular ultrasound results after radiation therapy and at follow-up. Thus, a combination of both serial intravascular ultrasound and careful angiography, which documents balloon, stent, and radiation source positioning, can fully assess the effectiveness of this modality of treatment.