Buruli ulcer (BU), an often-deforming skin ulceration caused by Mycobacterium ulcerans (MU), is now considered by the World Health Organization to be the third most common mycobacterium infection. However, the reservoir of MU in the environment and the epidemiology of BU are poorly understood. The disease is prevalent in riverine, slow-flowing and swampy areas of several tropical and subtropical regions of the world, especially in West Africa where the disease is rapidly increasing in incidence. This paper presents a review of published literature concerning epidemiology of, transmission and susceptibility to MU infection. It considers several endemic natural environments and their influence on infection.