The incidence of non-Hodgkin's lymphoma (NHL) in elderly patients has increased in recent years. Approximately 36% of elderly patients with NHL are diagnosed with diffuse large-cell lymphoma (DLCL), an aggressive lymphoma subtype. Some authors have suggested that lymphoma in the elderly is intrinsically different from that seen in younger patients. Diffuse large-cell lymphoma, for example, is curable in about 50% of patients younger than 65 years of age but has a significantly lower cure rate in older subjects. Elderly patients with DLCL represent a group that is difficult to treat because of comorbidity, diminished organ functions, altered drug metabolism, and irregular drug clearance rates. These factors must be carefully considered when evaluating treatment options for older patients. The quality of life (QOL) associated with various regimens should obviously be evaluated, though QOL has so far received little attention in clinical trials. Analyses of the results from numerous phase II and phase III trials in patients with advanced aggressive NHL have demonstrated that overall survival is reduced when chemotherapy regimens more toxic than CHOP (cyclophosphamide/doxorubicin/ vincristine/prednisone) are employed, whereas therapeutic regimens that are less toxic are often less effective. CHOP, therefore, may be regarded as the current gold standard of therapy for elderly patients with DLCL. The addition of granulocyte colony-stimulating factors to CHOP chemotherapy is recommended to limit myelosuppression. Intensive chemotherapy followed by autologous stem cell transplantation has recently been extended to patients older than 60 years, with encouraging results, albeit in a highly selected groups of patients. Other promising lymphoma treatments with improved toxicity profiles are being developed. Clinical trials are recommended to determine if these new therapies are safe and active in elderly patients with DLCL.