The innate (genetically based) tolerance to the disease (the so-called trypanotolerance) is a phenomenon present in some African cattle and small ruminant breeds. Trypanotolerance is defined as the ability to survive and to be productive in tsetse infested areas without the aid of Trypanosomosis treatment while other breeds succumb to the disease.

Trypanotolerance is usually attributed to the African Bos taurus taurus breeds of cattle, particularly the N’Dama and the West African Shorthorn, present mainly in West and Central regions of Africa. Farming of disease-tolerant genotypes is one of the options for limiting the disease impact on animal health and production that has yet to realize its full potential. The exploitation of the so-called trypanotolerant breeds has been practiced for centuries as major, if not the only, option to sustain livestock production in 19 countries in the humid parts of West and Central Africa. However, trypanotolerance is a feature of only a third of the cattle in tsetse infested Africa, and of no more than 10% (or 15 million) of the cattle population south of the Sahara.

Limitation to fully exploit these breeds can be attributed largely to the belief that they are not productive because of their smaller size compared with most zebu types (Bos taurus indicus), and to the view that their trypanotolerance is effective only against local trypanosome populations. These views are still debated. It is generally admitted, however, that the trypanotolerant feature constitutes a valid option for animal production in tsetse infested areas and it is an element of the integrated pest management approach.