ETHNOPHARMACOLOGICAL RELEVANCE: This study reports on the uses of medicinal plants and ethnobotanical significance of Mt. Rtanj, Eastern Serbia. The aim of the study was collecting information on plant utilization and creating the list of medicinal plants collected by local community in the region of Rtanj Mt. in Serbia. METHODOLOGY: A group of generally elderly people from the region were interviewed, asked to identify a certain number of plant taxa used against various human ailments. A quantitative ethnobotanical comparison has been performed in relation to other studies concerning the central Balkan Peninsula. RESULTS: There is an inventory of 45 plant species recorded. At the family level, the most common in traditional usage were species of Labiatae (22%), Rosaceae (20%) and Compositae (13%). The results of the survey suggested that Hypericum perforatum was the most popular medicinal plant. Among the 7 different recorded types of preparation, the aerial parts of plants were the most popular (47.3%). The most frequently reported medicinal uses of herbal drugs include remedies for immune system (22.97%), respiratory system (15.77%) and digestive system disorders (15.32%). However, a comparatively small number of available plant species was used for medicinal purposes while the level of ethnobotanical diversity was lower when compared to adjacent regions. CONCLUSIONS: Ethnobotanical knowledge in this area is decreasing due to high emigration rates during the last period. The historically developed ethnobotanical heritage should be preserved and promoted on the larger level, getting the special position in the future management plans for this area.