Rituximab is a chimeric human/mouse monoclonal antibody that is approved for the treatment of relapsed and refractory non-Hodgkin's lymphoma (NHL) and in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy as first-line therapy for diffuse large B-cell NHL, where it has shown the first survival advantage over CHOP alone in more than 20 years. Strategies to help define the optimal therapeutic usage of rituximab are being assessed, including first-line and maintenance or extended therapy, and the combination of rituximab with chemotherapy in indolent NHL. Emerging data suggest that earlier use may yield higher response rates, extended therapy can prolong remission, and the addition of rituximab to chemotherapy can increase clinical and molecular remission rates when compared with those achieved using chemotherapy alone. Studies in the peritransplant setting suggest a role for rituximab in vivo purging prior to transplant and/or maintenance rituximab as a means of clearing minimal residual disease. Rituximab has also shown activity in other B-cell disorders such as chronic lymphocytic leukaemia. The full potential of this immunotherapeutic agent remains to be defined in ongoing and future clinical trials.