Clostridium difficile infection (CDI) is an emerging problem in terms of incidence, morbidity and mortality. Currently available treatment options are not always effective, especially in cases of recurrent/refractory or complicated CDI. The gut microbiota transplantation is a technique that has been sporadically practiced since the ‘50s, but its clinical efficacy has only recently been supported by scientific evidence. In the present article, we report the pathophysiological basis and the clinical indications of this technique that, in light of its low cost, and proven efficacy and safety, is likely to become part of the management guidelines of difficult cases of CDI in the near future.