Salvia divinorum is a hallucinogenic plant that is used for divination and spiritual communion by the Mazatecs of Mexico. The active component of the plant is salvinorin A, a neoclerodane diterpenoid that selectively acts as a potent κ opioid receptor agonist. Salvinorin A's novel receptor binding profile makes derivatives of the compound potentially useful in the treatment of various psychiatric and mood disorders. In this work, next generation sequencing (Roche 454) was used to generate a S. divinorum transcript database. Five distinct putative diterpene synthase cDNAs (two type II and three type I) were identified in the database. We report here a recombinant type II diterpene synthase capable of catalyzing the rearrangement of GGPP into terpentedienyl diphosphate (a neoclerodane diphosphate), and a recombinant type I diterpene synthase that renders terpentedienyl diphosphate into kolavenol. These enzymatic products are potential intermediates in the salvinorin A biosynthetic pathway.