Japanese encephalitis (JE) is a viral disease caused by a Flaviviridae virus. The virus follows an enzootic cycle for transmission, and the known vector in most of the cases is Culex species of mosquito, especially Cx. tritaeniorhynchus. However, proofs are there for direct transmission via oronasal dropping of infected animals and birds. The domesticated pigs and wading birds are the major reservoirs or amplifier hosts of the JE virus in which the virus grows and divides but does not produce any major symptoms or casualty. While humans and horses are considered as dead-end hosts since they do not contribute to further transmission of the virus, they may develop neural complications. The disease has been reported to be prevalent and critical especially in children. Japanese encephalitis has been a major health concern in Southeast Asia and Western Pacific regions for decades, and about 3 billion people are continuously living under risk. More than one JE virus genotype has been identified in circulation throughout the endemic regions that may impose distressing conditions in future. The extensive and continuous vaccination drives in countries like Japan and South Korea have lowered down the JE cases, but other developing countries still need strong and dedicated strategies to eradicate the disease. Integrated management and research are required to understand the host-vector-pathogen interactions and the factors that affect JEV transmission, specificity, emergence and re-emergence, and genotype shift.