The epidemiological factors associated with the development and spread of drug-resistant malaria have been recently explored by Wemsdorfer in a paper in which he looked at parasite-drug-human-vector interactions that affect the occurrence and dynamics of drug resistance. The question that decision-makers must be asking themselves, as we face the 21st century, is: how will we live with drug resistance? Allan Schapira, Peter Beales and M. Elizabeth Halloran are ideally placed to consider this question. Extracting lessons from the past, they focus on drug-resistant Plasmodium falciparum in Africa. They propose a mathematical model, which will improve the conceptual basis for policy decisions and which has implications for drug development as well as for malaria-control programmes.