Most countries in resource-poor, malaria-endemic areas lack current and comprehensive information on antimalarial drug efficacy, resulting in sub-optimal antimalarial treatment policies. Many African countries continue to use chloroquine despite very high rates of resistance, and others have changed policies based on limited data, with mixed success. Methods for measuring antimalarial drug efficacy and resistance include in vivo studies of clinical efficacy and parasitological resistance, in vitro susceptibility assays and molecular markers for resistance to some drugs. These methods have the potential to be used in an integrated fashion to provide timely information that is useful to policy makers, and the combined use of in vivo and molecular surveys could greatly extend the coverage of resistance monitoring. Malawi, the first African country to change from chloroquine to sulfadoxine/pyrimethamine at the national level, serves as a case study for resistance monitoring and evidence-based antimalarial policies. Molecular, in vitro and in vivo studies demonstrate that chloroquine-sensitive parasites reemerged and now predominate in Malawi after it switched from chloroquine to sulfadoxine/pyrimethamine. This raises the intriguing possibility of rotating antimalarial drugs.