In late 2006 an unusual ulcerative condition in wild fish was reported for the first time in Africa from the Chobe and upper Zambezi Rivers in Botswana and Namibia. Concern increased with subsistence fishermen reporting large numbers of ulcerated fish in their catches. In April 2007 the condition was confirmed as an outbreak of epizootic ulcerative syndrome (EUS). The causative agent, Aphanomyces invadans, is a pathogenic water mould of fish that shows little host specificity. Ulcers follow infection of tissues by oomycete zoospores, resulting in a granulomatous inflammation associated with invading oomycete hyphae. Granulomatous tracts surrounding oomycete hyphae within the necrotic tissues characterise the diagnostic histological picture. The upper Zambezi floodplain at the confluence with the Chobe River spans the four countries of Botswana, Namibia, Zambia and Zimbabwe, making disease control a challenge. The floodplain ecosystem supports a high fish diversity of around 80 species, and is an important breeding and nursery ground. The annual cycle of flooding brings about changes in water quality that are thought to favour the infectivity of A. invadans, with diseased fish appearing soon after the plains become flooded. Since 2006 the disease has spread rapidly upstream along the upper Zambezi and its tributaries. By 2010 the disease was reported from the Okavango Delta in Botswana and in 2011 from the Western Cape Province of South Africa. EUS has the potential to disrupt floodplain ecosystems elsewhere in Africa where high fish diversity forms the basis of subsistence fisheries and local economies, and is a direct threat to freshwater fish culture.