Orthopedics is the branch of veterinary medicine concerned with the diagnosis, treatment, and prevention of diseases and injuries related to the musculoskeletal system, which includes bones, joints, ligaments, tendons, and muscles. In donkeys and mules, orthopedic issues can significantly affect their mobility, performance, and quality of life. Horse orthopedic issues are well documented in textbooks and peer reviewed manuscripts. Theoretically, since the species are similar, the same issues affecting horses can affect donkeys and mules, but that’s not always true. Understanding the unique anatomical and physiological characteristics of donkeys and mules is crucial for effective orthopedic care, as their musculoskeletal system differs in several ways from that of horses. This chapter explores the most common orthopedic conditions in donkeys and mules, diagnostic methods, treatment strategies, and preventive care practices to promote long-term musculoskeletal health.