The recent phase III intergroup trial showed no improvement in outcome with the use of second- and third-generation regimens for primary treatment of aggressive lymphomas. Efforts are now underway to significantly intensify therapies for patients with high-risk aggressive lymphoma by utilizing hematopoietic growth factors or autologous peripheral blood stem cells. Preliminary results show minimal or no benefit to intensification of standard regimens using growth factor support alone. However, high-risk patients who achieve a complete remission with standard therapy appear to benefit from consolidative bone marrow transplantation. Results of a novel, dose-intense regimen, which administers several non-cross-resistant drugs as high-dose single agents in rapid succession, may provide a promising alternative for primary therapy of high-risk aggressive lymphoma. New regimens incorporating high-dose cytarabine for patients with poor prognosis, small noncleaved-cell lymphoma seem to improve survival. The ability to effectively tailor therapy for subgroups of patients with aggressive lymphoma depends on the continued identification of clinical and biologic prognostic factors to compliment the International Prognostic Factors Index.