The authors reviewed a wide number of microbiological and medical papers outlining the profile of different probiotic strains in the immunemodulating activity related to major and minor clinical impairment of soluble and cell-mediated immunity. Starting from in vitro and experimental animal studies, a good number of clinical trials are reported, enclosing an update of the side effects of the probiotic long-term administration. Conclusively, the biological therapies are currently oriented to direct delivery of cytokines and molecules involved in the immune process enhancement. Using probiotics to sustain the immune response and to rescue the suppressed immunity is still a very modern approach, being also cheap and practical. This review thus highlights the rationale for this probiotic therapeutic indication which is largely safe and reliable.