After the eradication of smallpox (SPX), a new zoonotic threat that can trigger outbreaks has emerged. It may be fatal during the COVID19 outbreak. Humanity continues to be threatened due to re-emergence of the outbreaks. In most cases, new emerging viral agents originate from nonhuman hosts with zoonotic origins. Recent outbreaks of zoonotic infectious diseases with the potential to cause epidemics and pandemics continue to pose a major threat to the health security of entire regions, continents, and the world at large. Around five decades backthat Monkeypox (MPX) was reported for the first time in the Democratic Republic of the Congo (DRC) and was then confined to Central Africa only. Over the time, it has spread to other regions of Africa as well as outside Africa. As of August 2022, 40398 infections have been confirmed in almost 68 countries that have never reported MPX before. The majority of infections have been reported in Europe and Southeast Asia. On 23rd August 2022, MPX was declared a public health emergency of international concern, a step below declaring any disease as a pandemic. The article discusses the recent history of MPX outbreaks, as well as the evolving clinical manifestations of the disease, and the possible causes of the increase in cases, including the cessation of SPX vaccinations.