NF-kappa B is a pleiotropic transcription factor, which-regulates osteoclast formation, function, and survival. The finding that the deletion of both NF-kappa B p50 and p52 subunits resulted in osteopetrosis due to the absence of osteoclasts was followed by the observation that NF-kappa B is essential for RANK-expressing osteoclast precursors to differentiate into TRAP+ osteoclasts in response to RANKL and other osteoclastogenic cytokines. Thus, inhibitors of NF-kappa B should prevent osteoclast formation induced directly or indirectly by RANKL or TNF. In this mini review, we discuss the research findings that revealed essential roles of NF-kappa B signaling in osteoclasts. (C) 2008 Elsevier Inc. All rights reserved.