This chapter describes the current knowledge on various anesthetic and analgesic protocols, drugs and techniques for donkeys and mules. Although the number of publications in this field is steadily growing, there is still much information that is not available about donkeys and mules. At these moments, the veterinary practitioner must rely on own personal experience and also on knowledge and experience from anesthesia and pain management in horses. With this chapter, we aim to describe the scientific evidence on anesthesia and pain management in donkeys and mules and try to merge this into the general knowledge that we can extrapolate from knowledge in horses. Where possible, we will compare and contrast the choice for drugs, protocols and techniques in donkeys and mules with those for horses. Like for equine anesthesia, there are inherent risks involved with the use of anesthetics for donkeys and mules too, but we can make the anesthetic procedures as safe as possible with sufficient theoretical backgrounds and appropriate and careful monitoring of our patients.