Rituximab is the first monoclonal antibody to have been registered for the treatment of B-cell lymphomas. Randomized studies haves demonstrated its activity in follicular lymphoma (FL), mantle cell lymphoma and diffuse large B-cell lymphoma (DLBCL) in untreated or relapsing patients. Non-comparative studies have shown an activity in all other lymphomas. Because of its high activity and low toxicity ratio, rituximab has transformed the outcome of patients with B-cell lymphoma. A combination of rituximab plus chemotherapy, rituximab+ cyclophosphamide+ doxorubicin+ vincristine+ prednisolone (R-CHOP), has the highest efficacy ever described with any chemotherapy in DLBCL and FL. Some patients are refractory to rituximab but the precise mechanisms of this refractoriness are not understood.