BAFF, a member of the family of tumor necrosis factor ligands, is essential for the development of peripheral, mature, long-lived B lymphocytes. It binds to three different receptors (BCMA, TACI and BAFF-R), which are all members of the family of tumor necrosis factor receptors. Defects in the genes encoding either BAFF or BAFF-R abolish the generation of mature B cells. BAFF is made by myeloid cells while BAFF-R is expressed preferentially on B cells. BAFF induces polyclonal maturation of resting, short-lived immature cells to resting, long-lived mature B cells without proliferation. Lupus erythematodes-prone mice have elevated levels of BAFF in their blood, and treatment of these mice with BAFF decoy receptor (BCMA-Ig) prevents the onset of this autoimmune disease. Human lupus patients also show elevated levels of BAFF in their blood. Treatments with BAFF-neutralizing agents should prevent, delay or, at least, slow down the disease.