Until recently, national and global malaria control authorities recommended clinical diagnosis—based solely on the presence or history of fever—for most malaria treatment settings in sub-Saharan Africa where malaria transmission is sustained and intense. To some extent this recommendation was based on the fact that conventional antimalarial treatments like chloroquine or sulfadoxine-pyrimethamine (SP) were relatively affordable and safe and that microscopic diagnosis was complex and difficult to maintain in remote rural settings. It was economically advantageous and logistically more feasible to treat all potential cases as malaria than to extend microscopic diagnosis to every level of the health system. This approach has resulted in extensive over-treatment, particularly among older children and adults, and may have contributed to the rapid development of antimalarial drug resistance.