Hendra virus (HeV) and Nipah virus (NiV) form a separate genus Henipavirus within the family Paramyxoviridae, and are classified as biosafety level 4 pathogens due to their high case fatality rate following human infection and because of the lack of effective vaccines or therapy. Both viruses emerged from their natural reservoir during the last decade of the twentieth century, causing severe disease in humans, horses and swine, and infecting a number of other mammalian species. The current review summarizes our up to date understanding of pathology and pathogenesis in the natural reservoir species, the Pteropus bat, and in the equine and porcine spill over species.