Prior to the advent of biomedicine, rural communities in Nepal relied on phytochemically active compounds in medicinal plants as their primary source of medicine; however, ethnobotanical practices have shifted over time due to economic, environmental, and sociocultural stimuli. Findings from 2016 fieldwork conducted in Dumrikharka, Nepal and Tutung, Nepal are compared to existing literature to describe the political ecology of medicinal plants in rural Nepal. Anthropogenic climate change threatens individual plant species and ecosystem biodiversity. Globalized markets unabated by weak conservation programs place increasing demands on medicinal plants. As indigenous plants become overharvested and more difficult to access, Nepalis incorporate non-indigenous plants into the local pharmacopeia. Novel use of non-indigenous plants illustrates both the dynamic, resilient nature of traditional medicine systems and a loss of biodiversity. Social changes, including outmigration to other countries, notions of modernity, and preference for pharmaceutical drugs, reduce potential candidates to learn and preserve ethnobotanical knowledge. Waterborne pathogens caused by inadequate sanitation infrastructure continue to endanger Nepali populations. The dearth of clinical facilities throughout rural areas, when coupled with the decline ethnobotanical knowledge and traditional healers, poses a gap in healthcare jeopardizing vulnerable, marginalized populations. These factors reinforce the unequal distribution of resources in one of the world’s poorest countries, buttressing power inequalities and economic inequities.