The review summarizes the history of the emergence of the Henipviruses, provides a general introduction of their molecular biology and the efforts to develop antiviral treatment strategies, including the successful development of a veterinary vaccine. Paramyxoviridae, genus Henipavirus comprises emerging pathogens detected in Southeast Asia, Australia and Africa. Henipaviruses are enveloped with non-segmented, negative-sense, single-stranded RNA molecules and are distinguished from other Paramyxoviruses by a substantially larger RNA genome. Hendra virus (HeV) and Nipah virus (NiV) are the causative agents of zoonotic disease outbreaks in Australia and Asia, respectively, and are indigenous to fruit bats. HeV and NiV can cause severe diseases with neurological and respiratory manifestations in humans and intermediate hosts but do not cause a disease in the natural bat host. The primary spill-over reservoir for humans to come into contact with HeV in Australia and NiV in Malaysia are horses and pigs, respectively. Direct bat-to-human transmissions are reported from NiV infections in Bangladesh. The life cycle of the Henipaviruses includes replication of the RNA genome in the cytoplasm, a nuclear phase of the viral matrix protein, and assembly and budding of infectious virions at the cell membrane. To prevent the establishment of an antiviral cellular state, Henipaviruses encode structural and non-structural viral proteins able to antagonize the interferon type I response. For the development of antiviral treatments, strategies are under investigation to interfere with viral replication and entry, and finally to generate antibodies suitable for passive immunotherapy. A veterinary vaccine against HeV has been in use since 2012 to protect horses, and hence interrupts the transmission pathway to humans. The successful development of a veterinary vaccine based on a soluble HeV envelope protein may set the path for the development of an optimal vaccine against the medically relevant NiV. Henipaviruses are widely distributed, predominantly using fruit bats as their natural hosts. Their broad species tropism, the capacity to exploit different transmission pathways, and the ability to cause severe diseases in humans and intermediate hosts highlight the need for potent antiviral strategies or vaccines. The characterization of the viral gene products, interacting host factors and immune targets is essential for the development of antiviral strategies to be able to overcome the threat of these emerging pathogens.