Newcastle disease virus (NDV) has a worldwide distribution, causing lethal infection in a wide range of avian species. Affected birds develop respiratory, digestive and neurologic symptoms with profound immunosuppression. Mild systemic Newcastle disease (ND) infection restricted to the respiratory and neurological systems can be observed in humans and other non-avian hosts. Evidence of ND infection and its genome-based detection have been reported in Bovidae (cattle and sheep), Mustelidae (mink), Cercetidae (hamster), Muridae (mice), Leporidae (rabbit), Camelidae (camel), Suidae (pig), Cercophithecidae (monkeys) and Hominidae (humans). Owing to frequent ND outbreaks in poultry workers, individuals engaged in the veterinary field, including poultry production or evisceration and vaccine production units have constantly been at a much higher risk than the general population. A lethal form of infection has been described in immunocompromised humans and non-avian species including mink, pig and cattle demonstrating the capability of NDV to cross species barriers. Therefore, contact with infectious material and/or affected birds can pose a risk of zoonosis and raise public health concerns. The broad and expanding host range of NDV and its maintenance within non-avian species hampers disease control, particularly in disease-endemic settings.