The standard therapy for patients with aggressive lymphoma is cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, which achieves a complete response in more than 60% of patients but is curative in only about 40-50%. More aggressive and/or dose-intensified chemotherapy regimens have failed to provide significant survival advantages compared with CHOP, and may have higher toxicity. Rituximab, a chimeric monoclonal antibody to the CD20 antigen, is effective as monotherapy in aggressive lymphoma and in combination with chemotherapy has demonstrated high response rates in phase II trials. A scheduled interim analysis of a randomized, prospective trial comparing rituximab plus CHOP with CHOP alone in elderly patients with untreated diffuse large B-cell lymphoma has shown significantly better response rates and survival with rituximab plus CHOP compared with CHOP alone. These results represent the first significant improvement in overall survival over CHOP in aggressive lymphoma for over 20 years. The addition of rituximab was not associated with significant additional toxicity over that seen with CHOP alone. Ongoing studies are underway to establish whether the survival benefit of rituximab plus CHOP is seen in younger patient populations. Rituximab in combination with chemotherapy is also being evaluated as salvage treatment for patients who relapse after initial chemotherapy. In a preliminary analysis of a study in 50 patients with refractory or relapsed aggressive lymphoma, rituximab plus etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH) chemotherapy has demonstrated promising results when used as sole salvage therapy and as an induction therapy prior to autologous stem-cell transplantation, again without significant additional toxicity.