A high-throughput screen puts us on the road to protecting populations against malaria Despite considerable progress in combating malaria, it remains one of the world's most important infectious diseases, with 50% of the world population at risk of developing the disease and a mortality rate of ∼0.5 million annually ( 1 ). The lack of an effective vaccine and the relentless ability of the Plasmodium parasite responsible for malaria to develop drug resistance has contributed to the continuing disease burden ( 2 – 4 ). Artemisinin-combination therapies (ACTs) are the mainstay of current treatment regimens, but decreased effectiveness, particularly in Southeast Asia, threatens our ability to control this disease. A global effort to develop new drugs for the treatment and prevention of malaria is under way but not guaranteed to succeed ( 3 , 5 , 6 ). These efforts include a systematic attempt to target all life-cycle stages of the parasite to allow combination therapies to be developed, which are also likely to reduce the development of resistance. High-throughput screens (HTSs) designed to identify small drug-like molecules that prevent growth of blood-stage parasites ( 7 , 8 ) and target-based approaches have identified new compounds that are currently in preclinical development and/or various stages of human clinical trials for treatment of malaria ( 3 ). Missing from these efforts has been a high-throughput technology to find liver stage–specific chemotypes. On page 1129 of this issue, Antonova-Koch et al. ( 9 ) report an HTS effort that has filled this gap. They identify a substantial number of new chemical starting points with potent liver-stage antimalarial activity, promising a new capacity to feed compounds through the drug development pipeline for chemoprotection.