Monkeypox outbreak 2022 global map. Credit: The Innovation.

An unexpected global outbreak of monkeypox virus challenges our knowledge of this long-known pathogen and raises questions about the reasons for its re-emergence. Here, we discuss the unusual aspects of this outbreak and the urgency for a coordinated public-health strategy and present knowledge gaps on epidemiology and molecular epidemiology, clinical presentation, transmission, treatment, and prevention. Similar to other re-emerging viruses of the past decades, the current monkeypox outbreak highlights the fact that threats of emerging pathogens can only be addressed on a global scale by improving preparedness and control strategies in endemic countries before viruses re-emerge globally.