Approximately 30% to 40% of patients with diffuse large B-cell lymphoma (DLBCL) will have either primary refractory disease or relapse after chemotherapy. In transplant-eligible patients, those with disease sensitive to salvage chemotherapy will significantly benefit from high-dose therapy with autologous stem cell transplantation. The rationale for considering radiation therapy (RT) for selected patients with relapsed/refractory DLBCL as a part of the salvage program is based on data regarding the patterns of relapse and retrospective series showing improved local control and clinical outcomes for patients who received peritransplant RT. In transplant-ineligible patients, RT can provide effective palliation and, in selected cases, be administered with curative intent if the relapsed/refractory disease is localized. We have reviewed the indications for RT in the setting of relapsed/refractory DLBCL and provided recommendations regarding the optimal timing of RT, dose fractionation scheme, and treatment volume in the context of specific case scenarios.