This manual provides concise and up-to-date knowledge on 15 infectious diseases that have the potential to become international threats, and tips on how to respond to each of them. The 21st century has already been marked by major epidemics. Old diseases - cholera, the plague and yellow fever - have returned, and new ones have emerged - SARS, pandemic influenza, MERS, Ebola and Zika. These epidemics and their impact on global public health have convinced the world’s governments of the need for a collective and coordinated defense against emerging public health threats and accelerated the revision of the International Health Regulations (2005), entered into force in 2007. Another Ebola epidemic, another plague epidemic or a new influenza pandemic are not mere probabilities, the threat is real. Whether transmitted by mosquitoes, other insects, via contact with animals or person-to-person, the only major uncertainty is when and where they, or a new, but equally lethal epidemic, will emerge. These diseases all have the potential to spread internationally highlighting the importance of immediate and coordinated response. The diseases covered are: Ebola virus disease, Lassa fever, Crimean-Congo haemorrhagic fever, yellow fever, Zika, Chikungunya, avian and other zoonotic influenza, seasonal influenza, pandemic influenza, Middle-East respiratory syndrome (MERS), cholera, monkeypox, the plague, leptospirosis and meningococcal meningitis. Although originally developed as guidance for WHO officials, this publication is available to a wide readership including all frontline responders - communities, government officials, non-State actors and public health professionals - who need to respond rapidly and effectively when an outbreak is detected.