Buruli ulcer, caused by the pathogen Mycobacterium ulcerans, is a major mycobacteriosis that affects people in scattered foci in the third world. It is amongst the most neglected of diseases in terms of primary healthcare strategies. However, this is changing as the World Health Organization launches a number of major global initiatives. Recent progress includes the unraveling of the genetic structure of the pathogen, examination of the mechanisms of virulence and the role of chemotherapy in disease treatment and prevention of recurrence, together with strategies aimed at reducing the economic burdens placed upon healthcare budgets of poorer nations. This review focuses upon the recent developments and the understanding of the disease, with particular focus on potential chemotherapy.