Osteoarthritis (OA) has traditionally been considered a degenerative joint disease often initiated by biomechanical injury and its link to the aging process.Progress in molecular biology in the past 2 decades has profoundly increased our knowledge in the OA pathogenesis, especially in elucidating the role of the immune system in OA initiation and progression.It is now recognized that after the initial injury to the joint by genetic, metabolic or mechanical factors, the immune system perpetuates OA disease progression through the same inflammatory mediators that trigger the activation of immune response.Immunomodulation therapy holds great promises in the treatment of OA.The role of inflammation, innate immunity and possibly autoimmunity in OA progression, findings in favor of the inflammatory theory of OA, and recent developments in immunomodulation therapy will be reviewed in this presentation.