The threat, development, spread, and intensification of antimalarial drug resistance are posing tremendous challenges to malaria-control activities throughout the world. Fundamental aspects of these activities are the identification and promotion of safe and effective therapy for acute malarial illness. A major tool in providing guidance on appropriate therapy is the national malaria-therapy policy, which describes antimalarial drugs available for use in a given country, their relative efficacy, and how best to use them in a variety of settings, from the community to the referral hospital. This review describes some of the factors that need to be considered in the development of a national, antimalarial drug policy as well as those that have impeded timely development of national policies, especially in sub-Saharan Africa.