Inflammatory osteolysis is a relatively frequent and incapacitating complication of rheumatoid arthritis and multiple other inflammation-associated bone diseases. It is thought to operate through an ultimate common pathway of accelerated osteoclast recruitment and activation under the control of cytokines produced in the inflammatory environment. Over the past decade, there have been major advances in our understanding of the mechanisms of osteoclastogenesis. It is now clear that the interaction of receptor activator NF-κB (RANK) and its ligand, RANKL, plays a central role in osteoclast formation and activity. Therefore, understanding osteoclastogenesis offers new pathways for potential therapeutic intervention in inflammatory osteolysis. The success of anti-tumor necrosis factor-α and interleukin-1 therapy highlights the central role that these specific cytokines play in this disease. This review outlines our current understanding of the mechanisms mediating inflammatory osteolysis and highlights potential therapeutic strategies. © 2008 Elsevier GmbH. All rights reserved.