The presence of tsetse and trypanosomiasis (T&T) in vast areas of sub-Saharan Africa is a major constraint to livestock-agricultural development. However, the impact of the disease varies within and between countries, regions and agro-ecological zones. Therefore, prior to any intervention it is essential to evaluate the profitability of different approaches towards controlling the vector and/or the disease in each individual project or zone. This ensures that a project is assessed on its own merits and not merely on its possible technical contribution to a potential continent-wide programme. This paper has tried to cover the main methodological issues involved in the economic assessment of area-wide T&T control programmes, with particular reference to West Africa. The dynamics of benefits and costs over time have been examined, especially in relation to the densities of human and cattle populations. A conceptual model shows tsetse control costs falling with rising human populations. Benefits, however, initially rise and then peak when mixed farming is established but tsetse challenge persists. Also, benefits tend to fall when human populations rise to a level where the fly's habitat becomes eroded and/or high cropping intensity means that fewer cattle are kept. The economic analysis developed is used to characterize types of situations in West Africa where tsetse control is likely to be economically profitable and those where long-term area-wide projects are not likely to show good returns.