Abstract Background The district of Manang (2000 – 6000 m) is located in the Central Himalayas, Nepal. The majority of local inhabitants of the area are Gurungs, of Tibetan origin. The remoteness of the region has resulted in continued use of plants as medicine in an area where the ethnobotany has sparsely been documented. Methods Interviews were conducted with amchi (Tibetan medicinal practitioners), local healers (including priests locally known as 'lamas' ), plant traders, and knowledgeable villagers (including herders) regarding local plant names and their medicinal uses during several field visits (2002–2005). When convenient to the locals, a jungle or forest walk was done with the healers, allowing for both plant collection and detailed information gathering. Results This present research documented 91 ethnomedicinal plant species, belonging to 40 families under 73 genera, and 45 new ethnomedicinal plant species are added. These 91 locally used medicinal plants are found to treat 93 ailments. This study provides information on 45 plant species previously unknown for their medicinal uses in Manang. The indication for use, mode of preparation, dose and administration of medicine are described in detail for each species. Conclusion This wealth of ethnobotanical knowledge persists, and is being transferred to the next generation in some areas in upper Manang, in a country where this is often not the case. The senior amchi of the area (Karma Sonam Lama), who has been practicing Tibetan medicine for three generations, feels that it is of utmost importance to conserve the traditional healing system and to pass his knowledge on to the local community about the importance of medicinal plants. He hopes that this will lead to the conservation and sustainable management of medicinal plants in the villages. Over the duration of this research, the prices of several rare medicinal plants of Manang increased dramatically, highlighting both the scarcity and the quick disappear