Not all probiotics are created equal. The efficacy and safety of each probiotic microorganism has to be evaluated separately. This paper aims to systematically evaluate the effectiveness and safety of Saccharomyces boulardii in children and adults. The MEDLINE and The Cochrane Library (both up to June 2012) were searched for randomized controlled trials or their meta-analyses relevant to S. boulardii. Available evidence documents that S. boulardii is effective in treating acute gastroenteritis in children and preventing antibiotic-associated diarrhoea in children and adults treated with antibiotics for any reason. S. boulardii is probably effective in preventing Clostridium difficile infection and for the prevention of traveller’s diarrhoea. In patients with Helicobacter pylori infection, there is evidence to recommend the use of S. boulardii along with standard triple therapy as an option for increasing the eradication rates and decreasing overall therapy-related side effects, particularly diarrhoea.