Probiotic research is progressing rapidly with strong scientific-based observations. New molecular biologic techniques for the more accurate identification of intestinal microflora and seminal studies that have helped define the function of commensal bacteria in the gut have been reported recently. In functional terms, new techniques are operational to study the affect of microbial–host “crosstalk” between both bacteria and the host. Probiotics have been shown to initiate the activation of specific genes localized to these cells. Both the bacterial and host aspects of microbiota–host crosstalk can now be studied, in particular thanks to simplified in vivo gnotobiotic mouse models. Their functional genomic studies enable the screening for probiotic potential and for investigating the modulated expression of genes involved in a broad range of intestinal functions including regulation of nutrient uptake and metabolism, mucosal barrier and epithelial cell function, xenobiotic metabolism, and strengthening of the innate immune system. An important function of probiotics is its effect on the gut immune system. The latter may work by enhancing mucosal barrier function, preventing apoptosis of epithelial cells and ultimately, decreasing antigen uptake, especially in the small bowel. Clinically, there is strong evidence that some probiotics improve the digestibility of lactose and others prevent the recurrence of pouchitis after inflammatory bowel disease (IBD) surgery. There is reasonably strong evidence for the efficacy of probiotics in childhood infectious gastroenteritis and antibiotic-associated diarrhea. Recent data suggest the potential efficacy of probiotic strains in atopic eczema, IBD, Helicobacter pylori gastritis, neonatal necrotizing enterocolitis and as a substitute for inadequate initial neonatal colonization.