Over the past 15 years, we have learned that apparently localized non-Hodgkin's lymphomas of aggressive histologic subtypes are often microscopically disseminated diseases at the time of diagnosis, requiring systemic chemotherapy with doxorubicin-containing regimens to maximize the possibility of cure. This strategy results in cures for approximately 95% of stage I patients and 75% of stage II patients. There may be some additional benefit of consolidative radiotherapy following initial chemotherapy. In spite of these accomplishments, up to 30% of patients still fail treatment and die. We are currently unable to identify these patients prior to treatment, and additional empiric changes in the chemotherapy regimens are unlikely to further improve survival. Therefore, we need continued research aimed at increased understanding of the biology of non-Hodgkin's lymphomas.