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Poisonous animals imply a risk to human life, because their venom is a complex mixture of low molecular weight components, peptides and proteins. Hornets use the venom for self-defence, to repel intruders and to capture prey, but they can cause poisoning and allergic reactions to people. In particular, they seem to be a health problem in the countries where they are native due to their sting, which in the most severe cases can lead to severe or fatal systemic anaphylaxis. But this situation is being an emerging problem for new countries and continents because hornet incursions are increasing in the global change scenario, such as in Europe and America. Furthermore, 55 detailed cases of hornet sting were found in 27 papers during the current review where 36.4% died due to, mainly, a multi-organ failure, where renal failure and liver dysfunction were the most common complications. Moreover, the great taxonomic, ecological diversity, geographical distribution and the wide spectrum of pathophysiological symptoms of hornets have been the focus of new research. Considering this, the present systematic review summarizes the current knowledge about the components of Vespa venom and the epidemiology of its sting to serve as reference for the new research focused on the development of techniques for diagnosis, new drugs and treatments of its sting. [ABSTRACT FROM AUTHOR]