The tumor necrosis factor superfamily (TNFSF) member and cytokine known as B-cell activation factor belonging to the TNF-family (BAFF) has been identified as one of the key factors in the selection and survival of B cells. Overexpression of BAFF in mice leads to autoimmunity, whereas BAFF-deficient mice lack mature B cells. Although under normal concentrations of BAFF, non–self-reactive B cells survived and autoreactive B cells were deleted, a higher concentration of BAFF contributed to the survival of autoreactive B cells and elevated autoantibody production. Lupus-prone mice have increased serum levels of BAFF during the onset and progression of disease. The serum BAFF levels are elevated in patients with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome and ANCA-associated vasculitis, and showed positive correlations with autoantibodies. Based on the development of autoimmune disorders in animal models of BAFF overexpression and the elevated levels of serum BAFF in patients with autoimmune diseases, it appears that BAFF may be associated with autoimmune processes and that BAFF may be a potential biomarker for disease activity in autoimmune diseases. BAFF may also be important as a therapeutic target in those diseases and several BAFF-neutralizing agents are currently undergoing clinical trials.