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The malaria parasite, Plasmodium falciparum, has a demonstrated history of adaptation to antimalarials and host immune pressure. This ability unraveled global eradication programs fifty years ago and seriously threatens renewed efforts today. Despite the magnitude of the global health problem, little is known about the genetic mechanisms by which the parasite evades control efforts. Population genomic methods provide a new way to identify the mutations and genes responsible for drug resistance and other clinically important traits.