Several novel biologic therapies for rheumatoid arthritis (RA) are emerging that target aspects of the immune system other than tumor necrosis factor (TNF). Two such therapies currently in development include CTLA4Ig (Abatacept) and anti-CD20 monoclonal antibody (Rituximab). CTLA4Ig has been demonstrated to be well tolerated with a good short-term safety profile. Rituximab has also been shown to have a good safety profile in a limited number of RA patients. Further safety data with larger numbers of RA patients treated with Rituximab is required.