Sandalwood essential oil has been widely used not only as natural medicines but also in perfumery and food industries,with sesquiterpenoids as its major components including(Z)-α-santalol and(Z)-β-santalol and so on.The mature heartwoods of Santalum album,Santalum austrocaledonicum and Santalum spicatum are the major plant resources for extracting sandalwood essential oil,which have been overexploited.Synthetic biology approaches have been successfully applied to produce natural products on large scale.In this review,we summarize biosynthetic enzymes of santalenes and santalols,including various santalene synthases(STSs)and cytochrome P450 monooxygenases(CYPs),and then highlight the advances of biotechnological production of santalenes and santalols in heterologous hosts,especially metabolic engineering strategies for constructing santalene-and santalol-producing Saccharomyces cerevisiae.