The article reviews the emerging evidence that low-grade inflammation plays a critical role in the pathogenesis of osteoarthritis (OA). While OA has traditionally been viewed as a degenerative disease of cartilage, it is now recognized that the disease affects the entire joint structure, including the synovium, subchondral bone, and joint capsule. The inflammation in OA is distinct from that in rheumatoid arthritis and other autoimmune diseases, being chronic, low-grade, and primarily mediated by the innate immune system. Current treatments for OA only control symptoms and none have been FDA-approved for preventing or slowing disease progression. However, recent insights into the inflammatory underpinnings of OA offer promise for the development of new, disease-modifying therapies. The article discusses the molecular mechanisms of low-grade inflammation in OA, including the activation of pattern-recognition receptors by damage-associated molecular patterns, the role of the complement system, and the involvement of various inflammatory mediators such as cytokines, chemokines, and growth factors. It also explores the potential of anti-inflammatory therapies, highlighting the need for further research to identify effective inhibitors of low-grade inflammation and to determine whether these therapies can prevent or slow the progression of OA.The article reviews the emerging evidence that low-grade inflammation plays a critical role in the pathogenesis of osteoarthritis (OA). While OA has traditionally been viewed as a degenerative disease of cartilage, it is now recognized that the disease affects the entire joint structure, including the synovium, subchondral bone, and joint capsule. The inflammation in OA is distinct from that in rheumatoid arthritis and other autoimmune diseases, being chronic, low-grade, and primarily mediated by the innate immune system. Current treatments for OA only control symptoms and none have been FDA-approved for preventing or slowing disease progression. However, recent insights into the inflammatory underpinnings of OA offer promise for the development of new, disease-modifying therapies. The article discusses the molecular mechanisms of low-grade inflammation in OA, including the activation of pattern-recognition receptors by damage-associated molecular patterns, the role of the complement system, and the involvement of various inflammatory mediators such as cytokines, chemokines, and growth factors. It also explores the potential of anti-inflammatory therapies, highlighting the need for further research to identify effective inhibitors of low-grade inflammation and to determine whether these therapies can prevent or slow the progression of OA.