The study of probiotics and prebiotics is an expanding field of interest and scientific research that has resulted in insights related to the host immune response. Recent advances have naturally led to key questions. What are the specific probiotic components that mediate immunomodulation? Can we extrapolate the results of in vitro studies in animal and human trials? Which biomarkers and immune parameters should be measured in probiotic and prebiotic intervention studies? These questions were part of a discussion entitled "How Can Probiotics and Prebiotics Impact Mucosal Immunity" at the 2009 annual meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP). This review highlights recent knowledge about the modulation of mucosal immunity by probiotics and prebiotics, as well as considerations for measuring their effects on mucosal immunity. A list of biomarkers and immune parameters to be measured in human clinical trials is included.