Monkeypox has a relatively recent history. It was first discovered in monkeys in 1958, although a “vesicular disease in monkeys” was described in the1860s. The disease, and eventually the causative virus, was named monkeypox because the lesions (pox) seen in monkeys developed like other known pox-forming diseases (pustules that eventually break open, ulcerate, crust over, and some pox form scars in the skin). Later studies showed the “monkeypox” virus was actually sustained endemically in African rodents. It was not until 1970 in Africa (Zaire, now the Democratic Republic of Congo), when a 9-year-old boy (who developed smallpox-like lesions) was the first person to eventually be diagnosed with monkeypox. This situation initially caused concern that smallpox may also have an animal reservoir or endemic population that would make eradication of smallpox impossible. Fortunately, this was not the case because monkeypox was found to be a different species of pox virus, and smallpox was eradicated from the human population by vaccinations in 1979 (currently, only a few research labs have access to smallpox viruses). Monkeypox is now the major Orthopoxvirus that infects humans and fortunately, not frequently. However, vigilance is warranted as there have been several outbreaks of monkeypox since the 1970s. Although most have occurred in Africa (mainly western and central Africa), there was an outbreak in the U.S. in 2003. This apparently happened when an animal distributor either housed or transported monkeypox-infected African rodents (Gambian rats) with prairie dogs that were later purchased as pets, became “sick,” and transmitted the disease to their owners.