Camelpox virus (CMLV) causes a smallpox-like illness in a unique host, the camel. The disease is enzootic in almost all regions where camel husbandry is practiced, and is responsible for severe economic losses. Although it is genetically the closest known virus to variola virus, the etiologic agent of smallpox, CMLV remains poorly studied. It is characterized by a narrow host range, the capacity to induce giant cells in culture and to counteract host immune defenses; however, the genetic bases associated with these features are not understood. Also, it still needs to be demonstrated whether CMLV strains of variable virulence circulate and how arthropod vectors might be involved in virus transmission. Current evidence indicates that, under certain circumstances, CMLV can be mildly pathogenic in humans. A reservoir host other than camels is unlikely to exist. We review here current knowledge of CMLV, including clinical and laboratory aspects of the disease. We also discuss prevention and therapy by use of vaccines and antiviral treatments, as well as the possibility of camelpox eradication.