The normal stable flora of the gut of man and other adult animal species provides an effective barrier to infection by Clostridium difficile. Attempts to understand this mechanism have involved continuous flow and batch culture systems and colonisation of antibiotic pre-treated or germ free animals with gut flora from the same or unrelated species. In general attempts to re-create the barrier effect with the whole caecal or faecal flora have been successful both in vitro and in vivo, whereas attempts using components of that flora have not. The most recent developments in these types of studies have been studies aimed at understanding the mechanisms involved. Preliminary findings imply competition for various monosaccharides, especially those released from mucin, may be important.