Opioids have been used for centuries as antidiarrhoeal drugs. In recent years, their mechanism and sites of action in exerting their antidiarrhoeal effect have been studied intensely. Attempts have been made to propose their general mode of action. Whilst there are numerous similarities in their general effects on motility, fluid secretion, and neuroeffector transmission, the differences between species, in some cases, can be remarkable. We highlight and contrast the similarities and differences in the commonly examined species and compare them to humans. Insights into mechanisms of opioid antidiarrhoeal action now also provide some new perspectives of opioid action in the intestine.