Ethnopharmacological relevance: Our study shows that large parts of Vanuatu’s medicinal flora remain unexplored and that a high variability of medicinal plant knowledge between islands exists. Aim of the study: The following questions are comparatively analyzed for three islands of Vanuatu: who are the medicinal plant specialists and how important is their knowledge today? Which plants are used to treat common diseases? Materials and methods: On Loh, Ambrym and Aneityum plant related information was collected using semi-structured interviews, transect walks and participant observation. A total of 29 medicinal plant specialists were interviewed. Results: Medicinal plant specialists are either peasants or people with a high rank in the local social system such as members of the chief’s family or priests. Their knowledge may be very broad (Loh, Aneityum) or specialized on specific diseases (Ambrym). Medicinal plant knowledge is transmitted family and gender specific (Loh) or gender and family independent (Ambrym and Aneityum). Overall, 133 medicinal plant species were documented of which 117 are new to Vanuatu’s ethnopharmacopoeia. Mainly members of the Euphorbiaceae and Fabaceae, followed by Asteraceae, Convolvulaceae, Moraceae and Zingiberaceae are utilized. The majority of documented species are trees (33%), followed by herbs (22%) and shrubs (21%). Leaves accounted for the highest number of use reports (43%). The highest diversity of medicinal plants is found for the most common diseases such as skin, gastrointestinal, respiratory system and urogenital system diseases. Only a small overlap of taxa between the islands was found. Conclusions: The biocultural diversity of Vanuatu is reflected in the variability of medicinal plant knowledge and differences in the traditional medicinal system between the three islands investigated. Traditional medicine is more vital on remote islands. The better connected the islands are to the main city, the more dominant western medicine becomes and traditional medicine mainly remains to treat illnesses with a magical origin.