Human African Trypanosomiasis (HAT),which is also known as sleeping sickness, is a major cause of death and disability in 36 countries in sub-Saharan Africa. The disease is caused by the protozoan parasite of the Trypanosoma genus which is transmitted by the bite of the tsetse fly. The two types of HAT, the East African form due to Trypanosoma b.rhodesiensei (T. b.rhodesiensi) and the West African form due to T. b.gambiense, differ in their tempo of infection but in both cases the disease is always fatal if untreated. As well as multiple systemic features seen in the early (haemolymphatic) stage of disease, the late (encephalitic stage) stage, is associated with a wide range of neurological features including neuropsychiatric, motor and sensory abnormalities. Accurate staging of the disease is absolutely essential because of the potentially fatal complications of melarsoprol treatment of late-stage disease, the most important of which is a severe post-treatment reactive encephalopathy (PTRE) the pathogenesis of which is not fully understood. However, there is not a universal consensus as to how late-stage disease should be diagnosed using CSF criteria, and this has been very problematic in HAT. A more recent alternative drug for late stage gambiense disease is eflornithine (DFMO). There is a pressing need for a non-toxic oral drug for both early and late stage disease that would obviate many of the problems of staging, and various possible strategies to achieve this goal are currently underway. However, control of the disease will also require more effective measures of reducing man/fly contact and also the allocation of much greater financial and infrastructural resources than are currently available in Africa.