Sesquiterpenoids, derived from farnesyl pyrophosphate (FPP), comprise a large group of natural products with wide-ranging bioactivities in plants, animals, and microbes. Among these, artemisinin is the most renowned sesquiterpene-based drug used to treat malaria, but until now it could only be isolated from Artemisia annua plants. In this issue (pp. 1678-1688), Muangphrom et al. reveal a key factor controlling artemisinin biosynthetic capability and identify three novel sesquiterpene synthases from non-artemisinin-producing Artemisia species that are highly homologous to amorpha-4,11-diene synthase (ADS), the first committed gene in the artemisinin biosynthetic pathway. Functional analyses revealed that the ADS homolog in A. absinthium exhibits koidzumiol synthase activity, while those in A. kurramensis and A. maritima exhibit (+)-α-bisabolol synthase activity. These findings not only suggest a key role for ADS in controlling artemisinin biosynthetic capability, but also provide a significant advance towards artemisinin production in related species through metabolic engineering.