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Drugs have been used to prevent malaria for centuries, but only recently have they been used on a large scale to prevent malaria in the resident population of malaria endemic areas in sub-Saharan Africa. This paper discusses some of the reasons for the hesitancy in adoption of chemopreventive strategies in sub-Saharan Africa, reasons why this hesitancy has been overcome in recent years and the range of target groups now identified by the World Health Organization as those who can benefit most from chemoprevention. Adoption of carefully targeted chemopreventive strategies could help reverse the recent stagnation in the decline in malaria in sub-Saharan Africa that had been taking place during the previous two decades.