In the past, CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) was considered the gold standard treatment for aggressive non-Hodgkin's lymphoma (NHL). CHOP is only curative in approximately 40% of patients, and numerous clinical trials have been carried out to find a treatment that can increase the cure rate. For some patients with aggressive NHL, it is possible to improve survival by intensification of chemotherapy compared with standard CHOP. This approach is not appropriate for all patients, and careful patient selection is necessary to achieve benefit. Early high-dose treatment/autologous stem cell transplantation may be beneficial for some patients, but not in patients with low-risk disease or those over 60 years of age who are not eligible for autologous stem cell transplantation. The most striking and consistent improvement over CHOP chemotherapy in the treatment of aggressive NHL is the addition of rituximab. A phase III randomized study Groupe d'Etudes des Lymphomes de l'Adulte (GELA LNH 98.5) compared rituximab plus CHOP with CHOP alone in treatment of 399 patients aged 60 to 80 years of age with aggressive NHL. The addition of rituximab resulted in higher overall and complete response rates, and at a median follow-up of 3 years, event-free and overall survival were significantly higher in patients treated with rituximab plus CHOP compared with CHOP alone. The benefits of adding rituximab to CHOP were not restricted to a subgroup of patients, but were evident in patients with high- and low-risk disease. The addition of rituximab to CHOP also overcame bcl-2-associated resistance to chemotherapy. There is no standard chemotherapy regimen for relapsed patients, but results from several single-arm studies suggest the addition of rituximab will increase the complete response rate to many different salvage regimens. The development of newer treatment strategies incorporating rituximab may improve the cure rate further.