Japanese encephalitis (JE), the most important cause of epidemic encephalitis worldwide, is confined to Asia, but its geographical area is spreading. West Nile virus, and other closely related flaviviruses, cause similar disease elsewhere. Recent cryoelectron microscopic studies have characterized the flavivirus envelope protein as a new class of viral fusion protein (class II), and examined its arrangement on the virion surface. Changes in the envelope protein's hinge region, or its putative receptor-binding domain, are associated with changes in neurovirulence in animal models of JE. Clinically, JE causes a wide range of presentations, including a poliolike flaccid paralysis. Seizures and raised intracranial pressure are associated with a poor outcome, and may be potentially treatable. A safe efficacious formalin-inactivated vaccine against JE has been available for many years, but is too expensive for use in most Asian countries. A newer live attenuated vaccine has been used in China, but its use elsewhere has been restricted by regulatory concerns. A chimeric vaccine in which JE structural proteins are inserted into the 17D yellow fever vaccine backbone is one of several vaccines in development. There are no established antiviral treatments against JE. Interferon alpha was the most promising drug in small open trials, but a recent double-blind placebo controlled trial showed that it did not affect the outcome in children with JE.