B cells regulate immune responses during infectious, inflammatory and autoimmune diseases. Beside their unique and characteristic antibody production, B lymphocytes can modulate physiological and pathological processes by presenting antigens or synthesizing signaling molecules. In human and mouse diseases, immuno-intervention, targeting B cells, has revealed and highlighted their antibody-independent regulatory contribution. In this review, we focus on B cell-cytokine production, which is commonly disturbed in inflammatory disorders, and describe the B cell cytokine profile in different diseases. Finally, we discuss some key issues for future B cell-targeted therapies.