Probiotics are viable, nonpathogenic microorganisms (bacteria or yeast) which when administered in adequate amounts, confer a health benefit on the host. At this time, Saccharomyces boulardii is the only yeast commonly used in clinical practice. Literature on this probiotic is wide and even more data become available each year. Thus, it could be problematic for a physician summarize all the best information deriving from basic research and clinical studies. With the aim to help physicians in the use of Saccharomyces boulardii, this paper focuses on the available evidences for its efficacy and safety in different diseases in adult and pediatric patients in order to provide a practical guidance for gastroenterology clinical practice. Indications and dosage for several gastrointestinal diseases for a correct use of this probiotic are provided, and recent insights on its mechanisms of action and possible future clinical application are also discussed.