Inflammatory bone destruction is a relatively frequent and incapacitating complication of rheumatoid arthritis and other chronic inflammatory joint diseases, and is a product of acceleratesd osteoclast recruitment and activation in bone under the aegis of cytokines produced in the inflammatory milieu. Over the past decade there have been major advances in our understanding of the mechanisms of this family of diseases. It is now clear that p38 mitogen-activated protein kinase plays an essential role in the production of proinflammatory cytokines and cytokine-induced osteoclastogenesis, thus providing a potential tool for preventing pathologic bone loss. This review outlines our current understanding of the mechanisms mediating inflammatory arthritis and highlights potential therapeutic strategies targeting p3B mitogen-activated protein kinase. © 2008 Future Medicine Ltd.