Hepatitis E virus (HEV) is a positive-stranded RNA virus causing epidemic and sporadic acute hepatitis. It is now an established zoonotic agent with a global footprint. While the Old World HEV genotypes 1 and 2 are associated with large waterborne anthroponotic epidemics, the more recent genotypes 3 and 4 are responsible for the zoonotic burden. HEV isolates from pigs, wild boars, and deer closely resemble autochthonous human strains of HEV; they are found circulating rampantly all through the Western Hemisphere and parts of Asia, causing high seroepidemiological prevalence in their handlers and consumers. Animal experiments and cell culture systems have demonstrated the successful cross-species transmission of HEV. Chickens, rats, rabbits, mongoose, and cattle form an ever increasing list of animals associated with HEV. With no available vaccine, changes in food habits, hygiene, awareness, and rigorous surveillance backed with reliable diagnosis are the only reprieve.