All antimalarial drugs developed so far have eventually succumbed to resistance. There is a general belief that the more people that are exposed to an antimalarial drug, the more likely it is that resistance will emerge. Mass drug administration (MDA) is therefore considered a potent cause of antimalarial drug resistance. In this Personal View, I discuss the circumstances under which antimalarial MDA increases or decreases the risk of resistance. It is the total number of parasites exposed and their individual probabilities of survival and spread that determine the risk, not the number of people that contain them. In malaria-endemic areas, a substantial proportion of the community carries malaria parasites in their blood without being ill. Although many more people have asymptomatic than symptomatic malaria at any time, their parasite burdens are several orders of magnitude lower, and their host defence mechanisms are substantially more effective. Symptomatic infections with high parasite numbers are the most likely source of resistance emergence, so effective mass treatment that reduces the number of symptomatic cases of malaria and its transmission can reduce the threat of antimalarial resistance emerging and spreading in treated populations.