B cells play an important role in the pathogenesis of autoimmune disease. B cells not only produce pathogenic autoantibodies, but also present self-antigens to T cells and provide costimulatory signals for self-reactiveT cells. Recently, biologics have been tried in several autoimmune diseases as immune modulators with some promising results. Among them, several biologic agents that target B cells have led to improved patients’ outcomes and quality of life in patients with rheumatoid arthritis and systemic lupus erythematosus. These agents either deplete B cells by targeting B cell surface antigens, such as CD20 and CD22, or block B cell survival by inhibiting the activity of B cell survival factors, such as BLyS and APRIL. Initially, I discuss briefly the role of B cells in driving autoimmune diseases, and then focus on the efficacy and safety data of the B cell-targeted therapy in rheumatoid arthritis and systemic lupus erythematosus.