The re-emergence of foot-and-mouth disease (FMD) in Botswana is reported. The disease outbreak occurred in the Matsiloje Extension Area of Francistown veterinary district situated in the northeastern part of the country in an Office International des épízooties (OIE) recognized FMD free zone without vaccination. The disease affected cattle only and did not spillover into sheep and goats resident in the same extension area, as demonstrated by lack of seroconversion to FMD when tested. The virus isolate associated with the outbreak was identified as FMD virus; Southern African Territories (SAT) type SAT-2. The disease outbreak is discussed in relation to FMD outbreaks that have occurred previously within and outside Botswana.