Mycobacterium ulcerans, the causative agent of Buruli ulcer, was discovered by Australian scientists during the investigation of an unusual cluster of destructive skin ulcers affecting residents of the Bairnsdale region in the temperate Australian state of Victoria. The disease was also recognised from the 1950s in tropical far north Queensland where it is called Daintree ulcer or Mossman ulcer. There are other small pockets of transmission in coastal Queensland and the Northern Territory near Darwin but remarkably Buruli ulcer is almost entirely absent from New South Wales, the most populous Australian state. In Victoria, there has been a marked recent increase in cases of Buruli ulcer associated with the establishment of new endemic areas near Melbourne, almost 300 km west of the original endemic area near Bairnsdale. There is emerging evidence in Victoria that BU may be a zoonosis that first affects the local possum population and then spills over to humans living nearby. Biting insects, particularly mosquitoes, are likely mechanical vectors but there may be other pathways of transmission involved. Universal access to rapid diagnosis with PCR and availability of combination oral antibiotic therapy and surgery have improved outcomes for Australian patients with BU. However, some cases can still be severe and require complex and prolonged treatment.