The intestinal microbiota is recognized to play a role in the defense against infection, but conversely also acts as a reservoir for potentially pathogenic organisms. Disruption to the microbiome can increase the risk of invasive infection from these organisms; therefore, strategies to restore the composition of the gut microbiota are a potential strategy of key interest to mitigate this risk. Fecal (or Intestinal) Microbiota Transplantation (FMT/IMT), is the administration of minimally manipulated screened healthy donor stool to an affected recipient, and remains the major ‘whole microbiome’ therapeutic approach at present. Driven by the marked success of using FMT in the treatment of recurrent Clostridioides difficile infection, he potential use of FMT in treating other infectious diseases is an area of active research. In this Review, we discuss key examples of this treatment based on recent findings relating to the interplay between microbiota and infection, and potential further exploitations of FMT/IMT.