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The ability of malaria parasites to develop resistance is primarily due to the high numbers of parasites in the infected person\u2019s bloodstream during the asexual blood stage of infection in conjunction with the mutability of their genomes. Identifying the genetic mutations that mediate antimalarial resistance has deepened our understanding of how the parasites evade our treatments and reveals molecular markers that can be used to track the emergence of resistance in clinical samples. In this review, we examine known genetic mutations that lead to resistance to the major classes of antimalarial medications: the 4-aminoquinolines (chloroquine, amodiaquine and piperaquine), antifolate drugs, aryl amino-alcohols (quinine, lumefantrine and mefloquine), artemisinin compounds, antibiotics (clindamycin and doxycycline) and a napthoquinone (atovaquone). We discuss how the evolution of antimalarial resistance informs strategies to design the next generation of antimalarial therapies.<\/jats:p>","DOI":"10.1093\/bfgp\/elz008","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T07:12:40Z","timestamp":1555398760000},"page":"314-328","source":"Crossref","is-referenced-by-count":97,"title":["The genomic architecture of antimalarial drug resistance"],"prefix":"10.1093","volume":"18","author":[{"given":"Annie N","family":"Cowell","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Global Health, Department of Medicine, University of California, San Diego, Gilman Dr., La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A","family":"Winzeler","sequence":"additional","affiliation":[{"name":"Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, Gilman Dr., La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,23]]},"reference":[{"key":"2019111808201698700_ref1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S1473-3099(03)00657-1","article-title":"Measurement of trends in childhood malaria mortality in Africa: an assessment of progress toward targets based on verbal autopsy","volume":"3","author":"Korenromp","year":"2003","journal-title":"Lancet Infect Dis"},{"key":"2019111808201698700_ref2","volume-title":"Artemisinin and Artemisinin-Based Combination Therapy Resistance","author":"World Health Organization","year":"2017"},{"key":"2019111808201698700_ref3","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/d41586-018-05772-z","article-title":"How to defuse malaria\u2019s ticking time 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