Hoof diseases represent a major welfare concern and productivity challenge for donkey and mule populations worldwide. These often stoic animals, historically used as beasts of burden, are prone to hoof-related conditions such as laminitis, white line disease, abscesses, keratomas, navicular syndrome, and flexor contractures. Despite their rugged appearance and ability to mask pain, donkeys and mules frequently present with advanced hoof pathology due to neglect, inadequate farriery, and lack of early veterinary intervention. Anatomical distinctions—including a more upright hoof conformation, thicker sole, and distinct frog position—require tailored management approaches, particularly in response to environmental challenges such as moisture, poor footing, and nutritional imbalances. This chapter provides a comprehensive overview of donkey and mule hoof anatomy, biomechanics, and disease management, emphasizing the role of radiographic and venographic imaging in diagnosing subtle or internal lesions. Biomechanical imbalances, such as altered hoof-pastern axis and mediolateral deviations, often contribute to chronic lameness and structural failure. A four-point trimming approach, modeled after the natural wear pattern of the donkey and mule hoof, is advocated to reduce leverage while maintaining sole depth and functional loading zones. Preventive care—including routine farriery, proper environmental hygiene, and nutritional regulation—is essential to improving long-term hoof health. In low-income regions where these animals remain vital to livelihoods, the high prevalence of hoof-related lameness further underscores the need for education, accessible veterinary services, and structured hoof care programs. By integrating clinical experience with peer-reviewed literature, this chapter aims to provide veterinarians, farriers, and caretakers with practical tools and strategies to improve outcomes and reduce suffering in these often underserved equids.