Arbovirus encephalitis acquired within Australia, also known as Australian encephalitis (AE), is a potentially fatal disease of humans usually caused by the mosquito-borne flavivirus Murray Valley encephalitis virus (MVE). Occasional cases have been caused by the closely related Kunjin virus (KUN) but these tend to be less severe and the disease is now usually referred to as Kunjin virus disease. These viruses are usually active in northern Australia during the wet season (December to May) and MVE is known to be enzootic in the north Kimberley region of Western Australia (WA) and in the Top End of the Northern Territory (NT). Culex annulirostris skuse is the major vector of both MVE and KUN and ardeid waterbirds are thought to be the main vertebrate hosts. During the 2000 wet season, northern and central Australia experienced exceptional weather conditions with record rainfall recorded in many areas. This led to extensive mosquito breeding, increased MVE transmission in the region and resulted in a number of MVE and KUN encephalitis cases being recorded from both WA and central Australia (southern NT and northern South Australia). An overview of the environmental conditions leading to this outbreak, vector numbers, results of sentinel chicken monitoring programs, symptoms and outcome of confirmed cases, and predictors for future outbreaks are presented in this paper.