Monkeypox virus (MPV) remains to hide in the equatorial rainforests of Central and West Africa over forty years after smallpox was eradicated. Monkeypox virus is one of orthopoxvirus subfamily, it's refers to a zoonotic disease caused by monkeypox virus (MPXV). Human monkeypox, on the other hand, has a much lower morbidity and fatality rate than smallpox. Reference to the current resurgence, monkeypox outbreaks have been reported over the past 5 decades. Ten (10) countries in Africa was initially discovered to be affected by the outbreak and subsequently 4 countries apart from Africa. Additionally, re-emergence of monkeypox in African countries, especially Nigeria about forty (40) years of the initial outbreak, midst 2010-2019. Climate change, deforestation, lack of proper health and research advance infrastructure among the society and uncontrol intake of bush meat in the African countries could have been the reason for the recent re-emergence of monkeypox within the communities. Public health significance of monkeypox outbreak could be the factors related to the vulnerability of the population towards monkeypox virus when smallpox vaccination was stopped.