The Eastern Himalayas and Indo-Burma are two unique global hotspots with rich floral and animal diversity and over 200 different human cultural groups. Most indigenous communities in northeast India still rely on the ancestral system of herbal medicine. Local cultures vary in their use of medicinal plants to treat similar diseases. This highlights the cross-cultural differences in resource exploitation among more than 70 tribes in eight states covering over 255,000 km2. This chapter examines popular and pharmacologically active plants, including Billi goat weed, Indian pennywort, East Indian glory bower, Fish mint, Indian trumpet tree, Toothache plant, Skunk vine, Guava, and Ginger, comparing these to 17 plants with moderately high consumption. Frequently used medicinal plant species are classified into very high, moderately high, low and very low benefit plants based on the number of tribes using them. Through phytochemical analysis and clinical testing, these plants have been confirmed to be medicinally useful, and their use can also provide livelihood for poor local communities. However, the resource use system in this region is relatively underdeveloped. Greater local involvement at higher levels in commercialization and changes in the current system of resource production could be beneficial. This outcome requires strong implementation of policies related to rural development and construction of infrastructure facilities. These findings contribute to knowledge about the dynamics of rural India and current development issues in multi-ethnic, ecologically diverse regions.