Historic outline of the development of drugs targeting B-cells.- Understanding B-cell biology.- Pharmacological effects and mechanisms of action of agents blocking B cells.- Systemic lupus erythematosus: direct B-cell blocking.- Systemic lupus erythematosus: indirect B-cell blocking.- B-cell targeted therapies in rheumatoid arthritis.- B-cell targeted therapies in Primary Sj?gren Syndrome.- Targeting B cells in ANCA-associated vasculitis.- B-cell targeted therapies in systemic sclerosis and inflammatory myopathies.- B-cell targeted therapies in cryoglobulinemia.- B-cell targeted therapies in autoimmune cytopenias and thrombosis.- Targeting B cells in neurological autoimmune diseases.- Targeting B cells in other systemic autoimmune diseases.- Safety of B-cell targeted therapies.- The future potential of biosimilars targeting B-cells.