BACKGROUND: Multiple lines of evidence now support the notion that gut microbiota can contribute to digestive and extra-digestive diseases. The emergence of these observations enabled to postulate a bacteria-centric paradigm to rethink the treatment of many diseases. The goal of therapy should not be to eradicate the flora but to modify it in a way that leads to symptomatic improvement; thus, the interest in the use of probiotics to modulate microbiota composition has increased worldwide in both community and healthcare settings. SUMMARY: The results of published studies are conflicting for most probiotic strains and formulations, and clinicians and consumers need a better understanding of probiotic risks and benefits. Currently, clear guidelines on when to use probiotics and the most effective probiotic for different gastrointestinal conditions are still lacking. Here, we reviewed the studies on the use of probiotics in some diseases of relevant interest to gastroenterologists, such as Helicobacter pylori infection, irritable bowel syndrome, and inflammatory bowel disease. Key Message: Although the evidence is relevant and promising for probiotics in general, and for specific strains and combinations of strains, it is not yet sufficient to draw unequivocal conclusions and clear recommendations.