A new study reports the existence of multiple populations of artemisinin-resistant Plasmodium falciparum parasites in western Cambodia, a known resistance hot spot. An analysis of genomic variation among 825 P. falciparum samples from a range of Asian and African locations revealed that there was higher genetic diversity between subpopulations in western Cambodia than is typically observed between parasite populations on different continents. Interestingly, three distinct artemisinin-resistant founder subpopulations showed evidence of recent expansion and were particularly enriched for SNPs in transporter genes and DNA mismatch repair genes. The discovery of multiple resistant subpopulations in this region suggests that there are several forms of P. falciparum resistance, and the identification of genetic markers for resistance is expected to assist malaria eradication efforts.