Summary: BAFF [B-cell activating factor belonging to the tumor necrosis factor (TNF) family] is a ligand that is required for peripheral B-cell survival and homeostasis. In addition to mediating B-cell survival, BAFF also regulates expression of certain B-cell-surface proteins, such as CD21/35. BAFF deficiency results in a reduced number of peripheral B cells and a diminished ability to mount robust humoral immune responses. Overexpression of BAFF has been linked to murine and human autoimmunity, and recent data provide clues as to how excess BAFF may allow the emergence of autoreactive B cells. In vivo animal testing with BAFF inhibitors has generated exciting data that support the pathway as a target for modulating B cells. The role of BAFF in B-cell biology, T-cell biology, and autoimmunity is discussed, as well as current efforts to develop BAFF inhibitors for clinical testing in autoimmune disorders.