Osteoarthritis (OA) is a chronic, low-grade inflammatory disease of the joint, characterized by cartilage degradation, bone remodeling, and synovial inflammation. Unlike rheumatoid arthritis, OA inflammation is primarily innate and not autoimmune. Current treatments only manage symptoms, not disease progression. Emerging evidence suggests that inflammation plays a central role in OA pathogenesis, involving immune cells, DAMPs, and complement activation. Inflammatory mediators such as cytokines, chemokines, and prostaglandins contribute to cartilage breakdown and joint damage. Targeting these inflammatory processes may offer new disease-modifying therapies. However, most anti-inflammatory treatments have not shown efficacy in OA clinical trials. Research into molecular mechanisms, including innate immune pathways, complement system, and inflammatory mediators, is crucial for developing effective therapies. Future studies should focus on understanding the complex interactions between inflammation and joint tissues to design targeted interventions that can prevent or slow OA progression.Osteoarthritis (OA) is a chronic, low-grade inflammatory disease of the joint, characterized by cartilage degradation, bone remodeling, and synovial inflammation. Unlike rheumatoid arthritis, OA inflammation is primarily innate and not autoimmune. Current treatments only manage symptoms, not disease progression. Emerging evidence suggests that inflammation plays a central role in OA pathogenesis, involving immune cells, DAMPs, and complement activation. Inflammatory mediators such as cytokines, chemokines, and prostaglandins contribute to cartilage breakdown and joint damage. Targeting these inflammatory processes may offer new disease-modifying therapies. However, most anti-inflammatory treatments have not shown efficacy in OA clinical trials. Research into molecular mechanisms, including innate immune pathways, complement system, and inflammatory mediators, is crucial for developing effective therapies. Future studies should focus on understanding the complex interactions between inflammation and joint tissues to design targeted interventions that can prevent or slow OA progression.