Clostridium difficile causes infectious diarrhoea in humans and animals. It has been found in both diarrhoeal and non-diarrhoeal pigs, horses, cattle and various other species, suggesting a potential reservoir for human infection. It has also been found in various meat products (beef, pork and turkey) in North America, and occasionally Europe, suggesting the possibility of food-borne transmission of C. difficile, although this has not been proven. PCR ribotype 078 is the most common ribotype of C. difficile found in pigs and cattle in the Northern Hemisphere. Recently there has been some overlap of animal and human ribotypes of C. difficile, particularly in areas of The Netherlands, and this has been confirmed by whole genome sequencing. In Australia, all production animals studied so far have harbored C. difficile (pigs, dairy calves and sheep), together with a high proportion of horses. However, ribotype 078 has not been detected (nor ribotype 027). Instead, calves and piglets are predominantly colonized by ribotypes 126, 127 and 033, with some common human ribotypes such as 014 present in piglets, together with unusual ribotypes seen only in Australia, such as 237. These results suggest that the epidemiology of C. difficile in animals in Australia is different to that in other parts of the world. Clearly, these strains may still pose a risk to humans, either through consumption of food or environmental contamination. The lower population density in this country may lessen the risk of the latter. The amplification of C. difficile in humans and animals is driven by antimicrobial use and if cephalosporins are driving C. difficile infection in animals in Australia, additional effort may be required to target cephalosporin use in veterinary medicine.