Malaria infects 300–500 million people and causes 1-2 million deaths each year, primarily children in Africa and Asia. More than half of the deaths occur among the poorest 20% of the world's population. One of the principal obstacles to addressing this global health threat is a lack of effective, affordable drugs. The chloroquine-based drugs that were used widely in the past have lost effectiveness because the Plasmodium parasite which causes malaria has become resistant to them. The faster-acting, more effective artemisinin-based drugs — as currently produced from plant sources — are too expensive for large-scale use in the countries where they are needed most. We have metabolically engineered E. coli to produce high levels of mono-, sesqui-, and diterpenes, most notably the sesquiterpene precursor to artemisinin, amorphadiene. The result of these studies is an E. coli host capable of producing 1,000,000-fold higher levels of amorphadiene than the strains and expression systems that had been available previously. The engineered strain contains a heterologous mevalonate-based terpene biosynthetic pathway and an amorphadiene cyclase gene resynthesized with the E. coli codon usage. Recently, we cloned the final steps in the artemisinin biosynthetic pathway and engineered yeast to produce artemisinic acid at high levels. The development of this technology will eventually reduce the cost of artemisinin-based combination therapies significantly below their current price.