There are only a few infections that cause disease and mortality in African buffalo. These include rinderpest (historically – now eradicated), anthrax, bovine tuberculosis, bovine brucellosis, bovine papillomatosis and possibly Rift Valley fever. Historically, buffalo were probably the original source and maintenance hosts of several important cattle diseases, namely the SAT strains of FMD and theileriosis caused by Theileria parva. More recently, cattle-adapted strains of these two diseases have evolved, and they now cycle in several areas of sub-Saharan Africa in the total absence of buffalo. Buffalo may also be important reservoirs of trypanosomes in tsetse fly-infested areas, and may be a source of heartwater rickettsias in open systems within the distribution range of the Amblyomma vector ticks. Buffalo are susceptible to a whole range of important livestock diseases, including bluetongue, epizootic haemorrhagic disease, peste des petits ruminants, bovine ephemeral fever, bovine viral diarrhoea and anaplasmosis, but large knowledge gaps remain. Although these pathogens can infect and replicate in buffalo, buffalo appear to play little or no role in the epidemiology and maintenance of these livestock diseases. Buffalo appear to be totally refractory to several important infections of livestock like lumpy skin disease, contagious bovine pleuropneumonia and dermatophilosis. Buffalo, like most wildlife species, naturally carry a complement of ecto- and endo- macroparasites. With few exceptions, most of these parasites do not appear to deleteriously affect the health of free-ranging buffalo in any way. They may, however, become a problem in intensive ranching systems.