Diarrhea and other gastrointestinal symptoms are possible side effects of long-term antibiotic therapy. The most common etiology of hospital-acquired diarrhea is Clostridium difficile infection (CDI). It has been demonstrated that probiotic use may be beneficial in the prevention of antibiotic-associated diarrhea. There is also growing evidence that a fecal microbiota transplant may reduce the duration and recurrence of CDI. In this review, we update the current knowledge on both modalities in the prevention of resistant CDI and as useful adjuncts to standard treatment.