While the COVID-19 pandemic rages on, the world is on high alert for a second public health threat: a global monkeypox outbreak. As a relative of smallpox, monkeypox, a zoonotic disease, used to restrict in Africa. However, a novel outbreak has been seen in Europe, a non-endemic region, since May 2022. In the face of this unprecedented event, there are specific vital facts concerning monkeypox that people should be aware of for global public health prevention and control, including pathogenetic and epidemiological aspects, as well as diagnostic issues. As the cases outside Africa are soaring and the large proportion of men have sex with man (MSM) population among them, it is imperative to think about the potential impacts on global public health, as well as the shifting epidemiological trend of monkeypox and the insight of this novel outbreak.