Trypanosomiasis occurs in domestic livestock in 37 countries in sub-Saharan Africa, and within most of these countries appears to be the most important disease constraint to livestock production. The disease is also a significant constraint to livestock production in parts of South America, the Middle East and the Far East In the absence of a vaccine for trypanosomiasis, administration of anti-trypanosomal compounds to livestock and control of the tsetse-fly vector are the primary methods used to control the disease in sub-Saharan Africa. However, because vector control is limited in application, chemotherapy and chemoprophylaxis are the predominant methods used to control the disease in most countries. At present the salts of isometamidium, homidium and diminazene are the only compounds recommended for use in cattle, sheep and goats. All three compounds have been on the market for at least 35 years and drug resistance appears to be an increasing problem. In contrast, the literature reviewed at the beginning of this thesis indicates that drug resistance does not appear to be a problem associated with the compounds recommended for use against the parasites causing theileriosis, babesiosis, anaplasmosis and cowdriosis, even though some of them have been used for as long as the anti-trypanosomal compounds. Drug resistance in trypanosomes appears to be an increasing problem associated with the current anti-trypanosomal compounds recommended for use in domestic livestock. Since it appears unlikely that new compounds will be developed in the near future, the long-term productivity of livestock in trypanosomiasis- endemic areas is dependent, at least in the near future, on maintaining the efficacy of these compounds. In this respect, the research described in this thesis was carried out, firstly, to develop methods to more accurately determine the prevalence and level of drug resistance in the field than is possible with other techniques. Secondly, much of the described research was carried out to characterise aspects of the epidemiology of drug-resistant infections, including definition of the role of various factors in development, maintenance and abrogation of drug-resistant infections in the field. Finally, a number of potential methods for controlling drug-resistant trypanosome infections were evaluated in vivo. In particular, integration of chemotherapy with vector control was shown to be a viable method for controlling multiple-drug resistant infections in cattle. (Abstract shortened by ProQuest.)