Foot and mouth disease (FMD) is endemic in African buffalo (Syncerus caffer) in the Kruger National Park (KNP) and surrounding game parks in South Africa. The last outbreak of the disease in domestic stock outside the FMD control zone occurred in 1957. Due to the success in containing the disease, the country was accorded zone freedom from FMD without vaccination by the Office International des Epizooties (OIE: World organisation for animal health) in 1995. This status was lost in September 2000 when the first-ever recorded case of serotype O in South Africa was diagnosed in a piggery in KwaZulu-Natal after the illegal feeding of untreated swill. In November 2000, an outbreak of FMD caused by serotype South African Territories (SAT) 1 was diagnosed in a feedlot within the free zone of Mpumalanga Province. The SAT 1 outbreak was traced to cattle in the FMD control zone south of the KNP after the game-proof fence surrounding the KNP was severely damaged by floods. This enabled buffalo to come into direct contact with cattle outside the KNP. A further outbreak caused by SAT 2 was diagnosed within the FMD control zone in February 2001, also as a result of buffalo having escaped from the KNP. All these outbreaks were successfully contained, with the re-instatement of zone freedom from FMD without vaccination by the OIE in May 2002. These outbreaks made it necessary to re-examine the methods of control and containment of FMD that have been practised for many years and which are in line with accepted international practices. The authors describe the rationale for the different control strategies that were followed, the need for a multidisciplinary approach to disease control, the interface between control and technological and diagnostic support and the lessons learned. Some suggestions for future control strategies are also offered.