This paper describes the first ethnobotanical study carried out with speakers of Iquito, a critically endangered language of northeastern Peru. The work examines significant changes the pharmacopoeia has undergone, developing a new measure, the Index of Plant Novelty (IPN) that combines oral history, linguistic, comparative ethnobotanical, and botanical data. Research was carried out in 2009 and 2010, with structured interviews and collection of 87 botanical voucher specimens in 39 botanical families. The study results suggest that no one single factor can fully explain the patterns of borrowing in the pharmacopoeia of San Antonio, although data show some support for previously proposed hypotheses that such borrowing fills gaps in the pharmacopoeia or that edible and ornamental plants are often adopted for medicinal use. However, this process must also be understood within the context of colonization by mestizo settlers, which has given higher prestige to uses and species from outside. A comparison between oral history data and the linguistic and comparative data suggests that the Iquito informants interviewed have underestimated the extent to which their current pharmacopoeia has been borrowed.