Monkeypox, a viral zoonosis caused by an Orthopoxvirus, is clinically characterized by fever, headache, lymphadenopathy, myalgia, rash and burdened by some complications that can be severe and life threatening. Monkeypox, endemic in some central and west African countries, in tropical areas near equator, rose to the headlines following its recent outbreak in non-endemic countries of Europe and the USA. Thus, the World Health Organization, worried about the growing dimension of the problem, declared monkeypox a global public health emergency. Now, after months of careful observation, the western scientific research is drawing conclusion that African endemic countries represent a reserve pool able to feed, through travelers and sexual networks, the outbreak in non-endemic countries in which high-risk communities such as gay and bisexual men are the most affected. Prevention through vaccination and early diagnosis are the core to breaking the chain of diffusion of this epidemic. Particular attention should be paid to avoid the spread from endemic countries, also implementing the economic investments in their public health system. Information campaigns and assistance to high-risk classes in non-endemic countries are important priorities, however, assuming that specific treatments for this disease are still tentative.