Antibiotics are among the most prescribed medications worldwide and they may cause an imbalance of the gut microbiota. At the same time, the incidence of Clostridium difficile diarrhea is increasing, with significant morbidity and mortality. Probiotics are living microorganisms, bacteria or yeasts, claimed to provide health benefits when ingested in sufficient quantity. Restoration of the gut microbiota has been evaluated as a means of preventing Clostridium difficile infection. The purpose of this article is to review the most recent evidence regarding the use of probiotics in the prevention of a first episode of Clostridium difficile infection among adult patients.