Whilst it is well-established that particular bacteria may cause gastroenteritis and other infections when present in the gut, it is only recently that we have made significant inroads into understanding the huge number of other bacteria and additional microbes that live within the gastrointestinal tract, referred to as the gut microbiome. In particular, we now recognise that bacteria within the gut microbiome have a wide variety of roles in maintaining different aspects of human health, and that disturbances of these bacteria may potentially cause or contribute to a number of different medical conditions, including particular infections, certain cancers, and chronic conditions including inflammatory bowel disease. Moreover, there is increasing awareness that these bacteria help determine how we respond to medication, including antibiotics and chemotherapy. There has been growing interest in different approaches to alter the gut microbiome as a novel approach to medical therapy. In this Review, we give an overview of the importance of the gut microbiome, with a particular focus upon critical care.