Donkeys (Equus asinus) and mules represent approximately 50% of the entire domestic equine herd in the world and play an essential role in the lives of thousands of people, primarily in developing countries. Despite their importance, donkeys are currently a neglected and threatened species due to abandonment, indiscriminate slaughter, and a lack of proper sanitary management. Specific knowledge about infectious viral diseases that affect this group of Equidae is still limited. In many cases, donkeys and mules are treated like horses, with the physiological differences between these species usually not taken into account. Most infectious diseases that affect the Equidae family are exclusive to the family, and they have a tremendous economic impact on the equine industry. However, some viruses may cross the species barrier and affect humans, representing an imminent risk to public health. Nevertheless, even with such importance, most studies are conducted on horses (Equus caballus), and there is little comparative information on infection in donkeys and mules. Therefore, the objective of this article is to provide a brief update on viruses that affect donkeys and mules, thereby compromising their performance and well-being. These diseases may put them at risk of extinction in some parts of the world due to neglect and the precarious conditions they live in and may ultimately endanger other species’ health and humans.