BACKGROUND: Chronic inflammation following knee injuries often results in persistent knee pain and post-traumatic osteoarthritis (PTOA). Understanding the inflammatory processes that follow a joint injury is crucial to effectively mitigate PTOA progression. While inflammation is an integral part of any healing response, unresolved, long-lasting inflammation can be detrimental to the joint. The resolution of inflammation is an active process coordinated by pro-resolving molecules, including specialized pro-resolving mediators (SPMs). While SPMs have been primarily studied in chronic inflammatory diseases, their role in degenerative knee conditions such as PTOA remains underexplored. METHODS: This review examines the process of inflammation and its resolution following knee joint injuries and subsequent PTOA, with a focus on the impact of SPMs. CONCLUSIONS: SPMs play a key role in the resolution of inflammation and may offer potential benefits in the management of knee injuries to improve pain and prevent PTOA.