Abstract: As a unique species of equine, the donkey has certain specific variations from the horse. This review highlights the origins of the donkey and how this impacts on its behavior, physiology, and propensity to disease. The donkey is less of a flight animal and has been used by humans for pack and draught work, in areas where their ability to survive poorer diets, and transboundary disease while masking overt signs of pain and distress has made them indispensable to human livelihoods. When living as a companion animal, however, the donkey easily accumulates adipose tissue, and this may create a metabolically compromised individual prone to diseases of excess such as laminitis and hyperlipemia. They show anatomic variations from the horse especially in the hoof, upper airway, and their conformation. Variations in physiology lead to differences in the metabolism and distribution of many drugs. With over 44 million donkeys worldwide, it is important that veterinarians have the ability to understand and treat this equid effectively.