B cells and antibodies play an important role in the alloresponse to renal grafts as well as in immune-mediated glomerular diseases. In transplantation, greater recognition and improved diagnosis of antibody-mediated rejection have been a catalyst to the introduction of newer drugs and regimens that target B cells, plasma cells, and donor-specific antibodies to improve the outcome associated with antibody-mediated rejection. In immune-mediated renal disease, novel and more selective B cell therapies are gradually modifying the traditional therapeutic approach that consists of steroids and other immunosuppressants. A new era of selective and more effective immunosuppression agents that target the humoral response is finally emerging in transplantation and renal diseases.