Therapy for aggressive non-Hodgkin's lymphomas has undergone significant evolution in the last 25 years. First generation combination chemotherapy studies produced complete remissions (CRs) of 45-53%, with 30-37% long term survivors. New treatment programs aimed at increasing CR rates were then developed with the assumption that the additional complete responders would also become long term disease free survivors. Initial reports of single institution pilot studies with third generation regimens suggested 68-86% CR and 58-69% survival; however, with longer follow-up, the survival decreased. Furthermore, confirmatory national Phase II trials using these newer regimens produced CR rates of only 49-65% and survival of 50-61%. Thus conclusions concerning the efficacy of these new regimens awaited the results of prospective randomized trials. The Southwest Oncology Group (SWOG) recently conducted a randomized trial comparing standard therapy, CHOP, to the third generation chemotherapy regimens, m-BACOD, ProMACE-CytaBOM, or MACOP-B. There is no difference in response rate, time to treatment failure, or overall survival between CHOP and the third generation regimens. However, the cost and toxicity levels of the new regimens were higher. Thus, CHOP remains the best available standard of care, but based on the finding that fewer than 50% of these patients are cured, SWOG believes that new treatment approaches for patients with advanced-stage aggressive histology non-Hodgkin's lymphoma must be developed.