Hepatitis E virus (HEV) is an underappreciated human and veterinary pathogen that circulates worldwide. Many strains within the Paslahepevirus balayani species do little clinical damage to their primary animal hosts yet are capable of transmitting to humans and causing severe disease under certain conditions. This makes HEV an important foodborne pathogen and as an occupational hazard for those who work in close proximity to animals. While a virus that appears innocuous to the primary host seems as though it should not be a priority pathogen, like most viruses, HEV has proven potential to mutate to forms with higher disease potential and enhanced host range. This is most evident in Paslahepevirus balayani genotype 3 strains that have acquired snippets of genetic material allowing for enhanced host range, in Rocahepevirus ratti species that have evolved to infect humans, and with the emergence of higher disease-causing strains of Avihepevirus magniiecur that have led to high losses in the poultry industry in China. Concerted efforts through a One Health approach are needed to understand HEV zoonosis and to mitigate potentially devastating future outbreaks.