The burgeoning problem of malaria in the developing world and the relentless march of drug resistance demand that we continue to seek new chemotherapeutic strategies. Given the enormous expense of developing and marketing new chemical entities, we often rely on an increased understanding of the pharmacology of older drugs and judicious use of drug combinations. Development is being driven primarily by public-private partnerships from academic investigations. Two such agents are the antifolate combination Lapdap, already licensed and soon to be combined with artesunate, and isoquine, a novel isoquinoline, about to enter clinical trials. Other drug combinations designed to minimize the spread of resistance are in the pipeline. Such developments are crucial as it becomes clear that existing drugs, even those used in combinations, may have limited lifetimes.