In the 126 years since it was first described, scientists have learned a great deal about Buruli ulcer, (an ulcerating skin infection caused by the environmental bacterium, Mycobacterium ulcerans), including how to treat it. Yet, there is 1 question about this neglected tropical disease that has remained unanswered: how is M. ulcerans transmitted to humans? In southeastern Australia, where Buruli ulcer is endemic and cases are increasing, researchers are putting together the M. ulcerans transmission puzzle. The more they learn, the better equipped they will be for managing infections.