Buruli ulcer is a skin disease caused by infection with Mycobacterium ulcerans, which produces a potent toxin known as mycolactone, thus distinguishing itself from all other mycobacterial diseases. Mycolactone destroys cells in the subcutis, leading to the development of large ulcers with undermined edges. The genome sequence of M ulcerans has now been published and it transpires that two identical copies of a plasmid carry the genetic code for mycolactone. The mode of transmission of infection remains uncertain, although environmental sources of the organisms are now better understood. Considerable progress has been made in understanding the immune response to M ulcerans and there have been major advances in management of the disease with the introduction of rational antibiotic therapy. We summarise the current understanding of M ulcerans and its relations with human beings.