It was in Sierra Leone, 100 years ago in 1899, that human malarial parasites were first observed in wild-caught Anopheles gambiae and An. funestus, the principal vectors of malaria in Africa. In the same year, Ronald Ross initiated the first antilarval measures for malaria control. This paper reviews 100 years of malaria field research and control in Sierra Leone, which became known as the 'White Man's Grave' in the 19th century largely because of the high malaria-related mortality amongst Europeans living there. The establishment of a field laboratory for the Liverpool School of Tropical Medicine in Freetown in 1920 made Sierra Leone the centre for malaria field research in Africa up to and during the Second World War. Eminent malariologists including Ronald Ross, Samuel Christophers, George Macdonald, Leonard Bruce-Chwatt, Brian Maegraith, Ian Macgregor, Brian Greenwood and Michael Service visited Sierra Leone for malaria-related activities. This review highlights the tremendous efforts made towards defining the epidemiological picture of the disease and the most effective means of combatting it. Malaria control in Sierra Leone, as in many other parts of the world, used to be based largely on mosquito eradication. However, experience gained over the past 100 years has shown that mosquito control is often not cost-effective in areas where the interruption of transmission cannot be sustained. Emphasis should now be on early diagnosis, treatment with effective antimalarials, and the selective use of preventive measures including vector control and insecticide-treated materials where they can be sustained.