The intestinal microbiota includes a diverse group of functional microorganisms, including candidate probiotics or viable microorganisms that benefit the host. Beneficial effects of probiotics include enhancing intestinal epithelial cell function, protecting against physiologic stress, modulating cytokine secretion profiles, influencing T lymphocyte populations, and enhancing antibody secretion. Probiotics have demonstrated significant potential as therapeutic options for a variety of diseases, but the mechanisms responsible for these effects remain to be fully elucidated. Accumulating evidence demonstrates that probiotics communicate with the host by modulating key signaling pathways, such as NFκB and MAPK, to either enhance or suppress activation and influence downstream pathways. Beneficial microbes can profoundly alter the physiology of the gastrointestinal tract, and understanding these mechanisms may result in new diagnostic and therapeutic strategies. © 2010 Landes Bioscience.