The definition of probiotics has evolved concomitant with a resurgence of research interest in host-microbe crosstalk. The original definition stated that the live active culture beneficially affects the host by improving its intestinal microbial balance, while current conceptions are based on target- and site- specific effects of clearly defined strains. The establishment of normal microbiota in the intestine represents a key process whereby the intestinal milieu is kept disease-free as it performs its dual function: mounting an inflammatory response to pathogens and maintaining hyporesponsiveness to innocuous antigens. Probiotic therapy is based on this concept of a healthy well-balanced gut microbiota. The probiotic performance of strains differs, however. Different bacteria have clearly defined adherence sites and immunological effects and divergent effects in the healthy versus inflamed mucosa. Hence, notwithstanding recent demonstrations of the important immunoregulatory potential of the healthy well-balanced gut microbiota, current probiotic research is directed towards identification of specific strains with anti-allergenic potential.