More than 61% of all human pathogens are zoonotic, representing 75% of all emerging pathogens during the past decade. Albeit significant technological leaps in diagnostics development and disease surveillance, zoonotic emerging infectious diseases are evermore a matter of concern, particularly in modern days where global warming keeps providing ideal climatic conditions to the introduction of exotic infectious agents or disease vectors in new territories. Worryingly, the 2019 novel coronavirus epidemic acts as an extreme reminder of the role animal reservoirs play in public health, accounting for over 4,200,000 deaths worldwide until today. In this Special Issue, we approach a myriad of zoonotic infectious diseases and their complex mechanisms. This Special Issue is composed of three reviews on zoonotic diseases of African Lions, hemogregarine classification, and hepatitis E virus in Brazil, followed by one letter and one opinion piece that broadens the spectrum of disease emergence to mechanistic aspects of emerging non-communicable diseases. The Special Issue is completed by six research papers covering a wide array of emerging and re-emerging diseases of poultry, bovine, poultry and tortoises, of various nature such as parasitic, bacterial, and viral. This is a brief but assertive collection that showcases the need to address health at the animal-human-environment interface, in a One Health perspective.