Orthopoxvirus is a genus of viruses in the family Poxviridae and subfamily Chordopoxvirinae. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated with this genus include smallpox, cowpox, horsepox, camelpox, and mpox. The most widely known member of the genus is Variola virus, which causes smallpox. It was eradicated globally by 1977, through the use of Vaccinia virus as a vaccine. The most recently described species is the Alaskapox virus, first isolated in 2015.

In May 2022, the World Health Organization (WHO) made an emergency announcement of the existence of a multi-country outbreak of mpox, a viral disease then commonly known as "monkeypox". The initial cluster of cases was found in the United Kingdom, where the first case was detected in London on 6 May 2022 in a patient with a recent travel history from Nigeria. On 16 May, the UK Health Security Agency (UKHSA) confirmed four new cases with no link to travel to a country where mpox is endemic. Subsequently, cases have been reported from many countries and regions. The outbreak marked the first time mpox had spread widely outside Central and West Africa. There is evidence that the disease had been circulating and evolving in human hosts over a number of years prior to the outbreak. The outbreak was of the Clade IIb variant of the virus.