Systemic lupus erythemaotsus (SLE) is an autoimmune disease involving multiple organ systems and characterized by anti-nuclear antibodies. While T cells and dendritic cells may play major roles in SLE, several lines of evidence strongly suggest a central role for B cells. This article will review the role of B cells in human SLE as well as the currently available data on the treatment of SLE by depleting B cells with anti-CD20 (rituximab).