Francois F Maree,1,2 Christopher J Kasanga,3, Katherine A Scott,1 Pamela A Opperman,1,2 Melanie Chitray,1,2, Abraham K Sangula,4 Raphael Sallu,3 Yona Sinkala,5 Philemon N Wambura,3 Donald P King,6 David J Paton,6 Mark M Rweyemamu,3 1Transboundary Animal Diseases Programme, Onderstepoort Veterinary Institute, Agricultural Research Council, Onderstepoort, Pretoria, South Africa; 2Department of Microbiology and Plant Pathology, Faculty of Agricultural and Natural Sciences, University of Pretoria, Pretoria, South Africa; 3Southern African Centre for Infectious Diseases Surveillance, Sokoine University of Agriculture, Morogoro, Tanzania; 4Foot-and-Mouth Disease Laboratory, Embakasi, Nairobi, Kenya; 5Department of Disease Control, School of Veterinary Medicine, University of Zambia, Lusaka, Zambia; 6The Pirbright Institute, Pirbright, Surrey, UK Abstract: The epidemiology of foot-and-mouth disease (FMD) in Africa is unique in the sense that six of the seven serotypes of FMD viruses (Southern African Territories [SAT] 1, SAT2, SAT3, A, O, and C), with the exception of Asia-1, have occurred in the last decade. Due to underreporting of FMD, the current strains circulating throughout sub-Saharan Africa are in many cases unknown. For SAT1, SAT2, and serotype A viruses, the genetic diversity is reflected in antigenic variation, and indications are that vaccine strains may be needed for each topotype. This has serious implications for control using vaccines and for choice of strains to include in regional antigen banks. The epidemiology is further complicated by the fact that SAT1, SAT2, and SAT3 viruses are maintained and spread by wildlife, persistently infecting African buffalo in particular. Although the precise mechanism of transmission of FMD from buffalo to cattle is not well understood, it is facilitated by direct contact between these two species. Once cattle are infected they may maintain SAT infections without the further involvement of buffalo. No single strategy for control of FMD in Africa is applicable. Decision on the most effective regional control strategy should focus on an ecosystem approach, identification of primary endemic areas, animal husbandry practices, climate, and animal movement. Within each ecosystem, human behavior could be integrated in disease control planning. Different regions in sub-Saharan Africa are at different developmental stages and are thus facing unique challenges and priorities in terms of veterinary disease control. Many science-based options targeting improved vaccinology, diagnostics, and other control measures have been described. This review therefore aims to emphasize, on one hand, the progress that has been achieved in the development of new technologies, including research towards improved tailored vaccines, appropriate vaccine strain selection, vaccine potency, and diagnostics, and how it relates to the conditions in Africa. On the other hand, we focus on the unique epidemiological, ecological, livestock farming and marketing, socioeconomic, and governance issues that constrain effective FMD control. Any such new technologies should have the availability of safe livestock products for trade as the ultimate goal.Keywords: vaccine, foot-and-mouth disease virus, vaccine matching, new-generation vaccine, diagnostic tests