A disaster is looming in Cambodia and the rest of the Greater Mekong subregion: A deadly malaria parasite has become resistant to both drugs used in the so-called artemisinin combination therapy, raising the specter of untreatable malaria. Exactly how big the threat is, and whether and how it might sweep through the region and beyond, are uncertain. But no one is taking any chances. The only way to avert that crisis, says a growing chorus of malaria researchers, international agencies, and donors, is to eliminate malaria completely from the entire region—and that means wiping out every single parasite. But no one has ever eliminated the disease in a place as socially and epidemiologically complex as the Mekong, and it is not at all clear they can pull it off. The stakes are high.