Clostridium difficile, a major cause of healthcare-associated diarrhea due to perturbation of the normal gastrointestinal microbiome, is responsible for significant morbidity, mortality, and healthcare expenditures. The incidence and severity of C difficile infection (CDI) is increasing, and recurrent disease is common. Recurrent infection can be difficult to manage with conventional antibiotic therapy. Fecal microbiota transplantation (FMT), which involves instillation of stool from a healthy donor into the gastrointestinal tract of the patient, restores the gut microbiome to a healthy state. FMT has emerged as a promising new treatment for CDI. There are limited data on FMT for treatment of primary CDI, but FMT appears safe and effective for recurrent CDI. The safety and efficacy of FMT in patients with severe primary or severe recurrent CDI has not been established. Patients with inflammatory bowel disease (IBD) who undergo FMT for CDI may be at increased risk of IBD flare, and caution should be exercised with use of FMT in that population. The long-term safety of FMT is unknown; thus, rigorously conducted prospective studies are needed.