Rituximab has improved the prognosis of patients with diffuse large B-cell lymphoma, but a high proportion of patients with advanced disease will relapse or will fail to achieve a remission with front-line treatment. Salvage chemotherapy, followed by high-dose chemotherapy or radiation therapy and autologous stem cell transplantation, remains the best treatment option for such patients, especially those who retain chemosensitivity. Allogeneic transplantation is under investigation in this setting, often as a treatment for relapse after autologous transplantation. Treatment-related mortality due to graft-versus-host disease, preparative regimen toxicity, and poor immune recovery often limits its benefits. This article reviews the role of hematopoietic stem cell transplantation in the treatment of diffuse large B-cell lymphoma, the incorporation of rituximab, and avenues of clinical investigation in this rapidly evolving field.