The CD20 antigen characteristic for mature B-cell is also expressed on B-cell Non-Hodgkin lymphomas (NHL). It thus presents a possible target for immunotherapy. NHL respond readily to radio- and/or chemotherapy but this standard treatment bears a high risk of relapse. The specific monoclonal anti-CD20-antibody Rituximab, the first to be approved for clinical use, could be shown to improve response rates, response duration, and survival in NHL when combined with standard therapy. This review details the development, clinical application, and future perspectives of anti-CD20-antibody treatment of NHL, thereby proving the efficiency of immunotherapy via targeting of a tumor associated antigen. (C) 2016 Elsevier Inc. All rights reserved.