There has been low level endemicity of Buruli ulcer (BU) - infection of subcutaneous tissue with Mycobacterium ulcerans - in some rural regions of Australia for decades. However, in the 1990s BU epidemiology changed and case numbers began to increase and occur around the major metropolitan city of Melbourne and the regional centre of Geelong in the state of Victoria, in southeast Australia. BU has been a notifiable disease in Victoria since 2004 and there has been on average 300 confirmed BU cases per year since 2017. Our research consortium has been attempting to address the key question of how BU is spreading from the environment to humans. We have made some important discoveries that implicate native possums as major wildlife reservoirs of the pathogen and mosquitoes as vectors. These findings have led to the first evidence-based opportunities to intervene in the transmission of BU.