This article reviews the current understanding of the processes driving the development and progression of inflammatory bowel disease (IBD), discusses how the dynamic crosstalk between resident microorganisms, host cells and the immune system is required in order to maintain immune homeostasis, and considers innovative strategies that allow the modification or modulation of the intestinal microorganismal community as a potential approach for treating IBD. This article next rationalizes the use of cell-based regenerative medicine as treatment for IBD, discusses the obstacles hindering its success, summarizes some of the results of recent clinical trials employing these therapies, and discusses ongoing work to enhance mesenchymal stem/stromal cells, making them better suited to the task of repairing the damage within the IBD gut.