The number of donkeys and mules throughout the world is stable, and awareness of their use and concern for welfare, pain recognition and treatment are receiving increasing veterinary interest. Therefore, accurate information about anaesthesia and analgesia in donkeys and mules is important to ever more equine practitioners. Since donkeys are physiologically and pharmacologically different from horses, knowledge on species specific aspects of anaesthesia and analgesia are very important. Mules combine elements from both donkey and horse backgrounds, leading to great diversity in size, temperament and body type. Physiologically, they seem to resemble horses more than donkeys. This review highlights the current knowledge on various anaesthetic and analgesic approaches in donkeys and mules. There is still much information that is not available about donkeys; in many circumstances, the clinician must use available equine information to treat the patient, while monitoring carefully to observe for differences in response to therapy compared to the horse.