Hendra virus (Henipavirus hendraense; HeV) is a zoonotic paramyxovirus that causes severe, fatal, respiratory, and neurologic disease, often with pyrexia, in horses in eastern Australia. Prototypic HeV (HeV-g1) was first identified in horses in 1994 and has since been identified in numerous equine outbreaks, whereas variant HeV (HeV-g2), which shares 83.5% nucleotide identity with HeV-g1, first emerged in 2015 and has only been identified in two horses. Pteropus bats (flying foxes) are the natural reservoir hosts of HeV, with transmission to horses mainly occurring through urinary excretion and resultant oronasal inoculation. Following infection, horses act as amplifying hosts, allowing for subsequent transmission to humans and domestic dogs. The majority (67.2%) of historical HeV outbreaks occurred in June to August, with the density of black flying foxes (P. alecto) and spectacled flying foxes (P. conspicillatus) predictive of outbreak locations. In the host, the G attachment glycoprotein of HeV binds to the primary cellular receptor, ephrin-B2, leading to activation of the fusion glycoprotein and subsequent cell entry or syncytial cell formation. Ephrin-B2 is expressed on endothelial cells, arteriolar smooth muscle, and neurons. Thus, HeV is vasculotropic, causing widespread vasculitis with endothelial syncytia and pulmonary edema, and neurotropic, causing meningoencephalitis. The gold standard method for diagnosis of HeV is rRT-PCR. The most effective method for prevention of equine and, by proxy, human HeV infection is equine vaccination. Today, HeV remains a formidable pathogen in horses and humans, representing a major, often fatal, occupational hazard for individuals in the equine industry, especially veterinary professionals.