The development of monoclonal antibodies has significantly affected the therapy of B-cell non-Hodgkin's lymphomas (NHLs). Rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, has activity in both indolent and aggressive B-cell lymphomas. Perhaps the greatest change has occurred in first-line therapy of advanced stage, diffuse large cell lymphoma (DLCL), where rituximab combined with conventional chemotherapy has improved both overall survival (OS) and progression-free survival (PFS) over combination chemotherapy alone. Further studies are needed assessing the role of rituximab in salvage therapy, as part of the conditioning regimen prior to autologous stem cell transplant, and as maintenance therapy for large cell lymphoma. Several novel monoclonal antibodies are in development and may also be active in DLCL. These agents may be most promising when combined with either chemotherapy or with rituximab. This review will summarize the use of rituximab in the therapy of diffuse large B-cell lymphoma and briefly describe antibodies in development.