Probiotics have been used in humans for almost a century and widely recommended for the treatment of a variety of ills assumed to be of colonic origin, including diarrhea, constipation, bloating, and flatulence. More recently, probiotics have been evaluated in the management of specific colonic disorders such as inflammatory bowel disease, irritable bowel syndrome, and Clostridium difficile colitis. It is evident that no two probiotics are exactly alike; why then should we expect reproducible results from studies that employ different species or strains, variable formulations, and diverse dosing schedules? When probiotics have been studied with the rigor appropriate to a new therapeutic modality, some coherent results have emerged: specific strains are effective in certain diarrheal states, irritable bowel syndrome, ulcerative colitis, and pouchitis, as well as in the prevention of C. difficile-related colitis. Even here, not to mention other colonic disorders, further adequately powered and appropriately designed trials are needed.