Despite the relative success of analogous approaches in soil, aquatic, and animal environments, the enhancement of human health through probiotic consumption has not been generally endorsed in modern medicine. Laboratory-based studies are elucidating the mechanisms that mediate the properties attributed to beneficial lactic acid bacteria and Saccharomyces species in vivo. This research is now providing fundamental evidence to support observations of adhesion of probiotic species to intestinal tissue, antimicrobial activities, and immunomodulation. Probiotics appear to have a promising future in the treatment of certain disorders. Rigorously performed, controlled, double-blinded trials will overcome doubts relating to efficacy in vivo and open avenues along which probiotic-based therapies will rapidly progress. As a result of our emerging understanding of microbial activities and gene expression in situ, novel strategies will combine complementary probiotic functionalities in the form of microbial consortia or genetically enhanced organisms. As scientific knowledge and biotechnologic proficiency advance at an accelerating pace, the requirement for informed legislation and for mechanisms of effectively delivering these therapies to the sites of their intended function may limit the applications of probiotics.