Treatment of inflammatory bowel disease at present mainly targets mediators of inflammation to stop or suppress pro-inflammatory processes. Typical examples are steroids, suppression of T cells by thioguanine nucleotides, or antibodies against cytokines such as tumour necrosis factor, interleukin 12, or interleukin 23. In addition to suppression of inflammation, development of therapeutic strategies that support resolution of inflammation or that actively resolve inflammation might be desirable. Resolution of inflammation is now seen as an active process involving specific mediators (eg, lipid mediators or specific cytokines) that is mandatory to restore organ function and completely shut down inflammation. The molecular pathways involved in resolution of inflammation have been investigated in recent years and could be adopted in treatment strategies for inflammatory bowel disease. Among these approaches are anti-integrin strategies and means to produce or locally increase restitution or resolution factors, such as restoration of the activity of transforming growth factor-β by anti-SMAD7 antisense oligonucleotides. The potential role of inflammation-resolving lipid mediators (eg, resolvins), however, still warrants further study and clinical development. This Review focuses on the specific role of active resolution of inflammation in inflammatory bowel disease pathophysiology. Potential therapeutic targets based on these pathways are also discussed.