Tsetse fly and African animal trypanosomosis (nagana) in South Africa provides an authoritative, in‑depth examination of the tsetse belt in northeastern KwaZulu‑Natal, the southernmost distribution of these vectors in Africa. This monograph traces the history of African animal trypanosomosis (nagana) from the mid‑1800s to 1990, detailing the disease’s impact on cattle health, productivity and rural livelihoods. The author presents comprehensive studies on the ecology of Glossina austeni and Glossina brevipalpis, including their distribution, abundance, dispersal patterns and seasonal activity in both game reserves and surrounding landscapes. Epidemiological analyses of the disease in cattle and African buffalo address vector competence, trypanosome prevalence, infectivity, virulence in experimental and field conditions, and results from an area‑wide survey of the tsetse belt. Control strategies and the socioeconomic significance of nagana are critically assessed, considering the effects of interventions on nontarget species, food chains, land use and ethics, culminating in a proposed socially just and technically feasible approach for sustainable management. This scholarly book highlights the urgent need for South African veterinary professionals and authorities to address nagana, a neglected animal disease that has been overlooked since 1990, with no official reporting or treatment programmes. It draws on original research conducted by the Agricultural Research Council–Onderstepoort Veterinary Research, integrating historical insights with contemporary scientific findings. This monograph serves as a vital resource for scholars, veterinarians, ecologists and policymakers, offering the most comprehensive account to date of tsetse ecology, disease epidemiology and sustainable control strategies in South Africa.