Although advanced, aggressive non-Hodgkin's lymphoma is highly responsive to chemotherapy, only approximately 30% of patients will have long-term disease-free survival and cure. Complex multiple-drug regimens have been claimed to be superior to standard regimens, eg, cyclophosphamide, doxorubicin, vincristine, and prednisone. However, several studies comparing this regimen with various multiple-drug regimens showed equivalent results with a more favorable toxicity profile for the standard regimen. Central nervous system lymphoma continues to carry a grim prognosis, but new approaches combining chemotherapy with radiation may lead to improved treatment. The availability of hematopoietic growth factors may help determine the role of dose intensity in the treatment of advanced, aggressive non-Hodgkin's lymphoma.