Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease that commonly affects the kidneys. It is characterized by persistent autoantibody production that targets a multitude of self-antigens. B-cells, plasmablasts and plasma cells, as the source of these autoantibodies, play a major role in the development of lupus nephritis (LN), and are therefore promising therapeutic targets. To date, however, randomized clinical trials of B-cell therapies in LN have not lived up to expectations, whereas uncontrolled cohort and observational studies of B-cell antagonists have been more promising. In this article, we will review the current experience with B-cell therapy in LN and highlight the pitfalls that may have limited their success. We will conclude by suggesting B-cell-centric approaches to the management of LN based on what has been learned from the overall B-cell experience in SLE.