NF-kappaB is a pleiotropic transcription factor, which regulates osteoclast formation, function, and survival. The finding that the deletion of both NF-kappaB p50 and p52 subunits resulted in osteopetrosis due to the absence of osteoclasts was followed by the observation that NF-kappaB is essential for RANK-expressing osteoclast precursors to differentiate into TRAP+ osteoclasts in response to RANKL and other osteoclastogenic cytokines. Thus, inhibitors of NF-kappaB 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-kappaB signaling in osteoclasts.