Gut dysbiosis has been identified as a potential factor that may drive a variety of diseases. Fecal microbiota transplantation (FMT) is a microecological therapy which delivers fecal microbiota of screened healthy donor into the recipient intestine. By restructuring the recipient gut microbiota with donor fecal samples, FMT has been used to treat a number of gastrointestinal and non-gastrointestinal disorders. Although FMT could cure 90% of recurrent C. difficile infections, the efficacy of FMT in other diseases is variable. These suggests that there are multiple factors influence the efficacy of FMT. This article will discuss the impact of both donor and recipient factors on donor microbiota engraftment and clinical efficacy in FMT.