The demonstration that immune and epithelial cells can discriminate between different microbial and bioactive plant species has extended the known mechanism(s) of action of nutraceuticals and probiotics beyond simple nutrition and/or antimicrobial effects. The progressive unravelling of these plant and bacterial effects on systemic immune and intestinal epithelial cell function has led to new credence for the use of probiotics and nutraceuticals in clinical medicine. Level I evidence now exists for the therapeutic use of probiotics in infectious diarrhea in children, recurrent Clostridium difficile-induced infections and post-operative pouchitis. Additional evidence is being acquired for the use of probiotics in other gastrointestinal infections, irritable bowel syndrome and inflammatory bowel disease. Not all individual probiotic strains have the same efficacy, and future clinical trials may focus on multistrain preparations agents with known efficacy. The use of nutraceuticals and probiotics as therapeutic agents for gastrointestinal disorders is rapidly moving into clinical usage. Scientific studies are providing mechanisms of action to explain the therapeutic effects, and randomized controlled trials are providing the necessary evidence for their incorporation into the therapeutic armamentarium.