Since the signing in 1987 of the Hemispheric Plan for the Eradication of Foot-and-Mouth Disease (PHEFA) by the countries of South America, clinical cases of foot and mouth disease (FMD) have decreased significantly throughout the continent. During the early 1990s, national laboratories diagnosed an average of 766 cases per year in South America. By the late 1990s, this continent-wide average had fallen to 130. By the end of the 1990s, the international community recognised Argentina, Chile, Guyana and Uruguay as free of FMD without vaccination. In 1999, clinical signs of FMD were absent in 60% of all cattle of the continent. These cattle represented 41% of all herds in South America and extended over 60% of the geographical area of the continent. However, in the spring of 2001, FMD re-appeared in certain countries of the Southern Cone. This widespread re-occurrence of the disease in Argentina, Uruguay and the State of Rio Grande do Sul in Brazil called into question the basic premise of the PHEFA – that countries in South America can achieve and maintain FMD-free status, with or without vaccination. The authors suggest that these countries can regain their FMD-free status by supporting the PHEFA. A successful disease eradication strategy relies on high levels of vaccination, effectiveness of outbreak responses, and control of animal movement. This strategy must have a regional, not national, focus and must be based on risk analysis methodology. The multilateral administration of vaccination campaigns and field activities to ensure wide and simultaneous vaccine application, along with primary prevention and joint border activities, is the key to eradicating FMD and maintaining areas free of the disease.