Abstract: BAFF (B cell activating factor belonging to the tumor necrosis factor family) is a vital ligand required for survival and differentiation of peripheral B cells. By interacting with three receptors, BAFF can promote B cell maturation and class switching, enhance humoral immunity and T cell co-stimulation. Over-expression of BAFF in mice leads to autoimmune diseases such as systemic lupus erythematosus (SLE). Treating the mice model of SLE with BAFF antagonists can ameliorate disease progression and enhance survival. Moreover, in some SLE patients serum level of BAFF is elevated and correlated with serum anti-dsDNA titer. The preliminary clinical trial of anti-BAFF monoclonal antibody has shown to be safe and effective. BAFF antagonists are promising therapeutic drugs for SLE.