Probiotics have been used for over a century, but their widespread application is still a matter of debate. Why are the reasons behind the probiotic conflict? Professor Bruno Pot focuses on the immune modulatory effects of probiotics, and by exploring how they modulate the immune system, clarifies the potential of these agents for treating immune disorders. Pot highlights the enormous body of work studying probiotics and immune function, and highlights some conflicting findings. Probiotics, for example, have been found to be useful for treating ulcerative colitis, but not Crohn’s disease. Why? Host genetic differences, as well as varying effects of different bacterial strains add a dimension of complexity to any study on probiotics.Pot reveals some fascinating biochemical mechanisms governing the anti-inflammatory process, such as the role of bacterial metabolites or the presence of factors within the bacterial cell wall that can elicit a pro- or anti-inflammatory response. The LS33 cell wall peptidoglycan is one example of a protective factor in models of colitis. In order to harness their full therapeutic potential, Pot counsels a realistic approach towards probiotics as adjunctive therapies rather than as superdrugs, and the use of mechanistic data as a platform from which to discover potential new modulators of immunity.