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Simple Summary: Increasing threats to wildlife have made assessing their populations, health, and adaptation to stressors ever more important. The use of environmental DNA to make these assessments is relatively new and offers many advantages, such as non-lethal sampling. How novel technologies such as these are framed in the news media is critically important because the general public gathers much of its information about scientific developments from the media, and public perceptions can impact use of technology, responses to data derived from its use, and ethical concerns. To date, media constructions of eDNA and perceptions among the general public have not been examined. The current paper begins to address this gap by undertaking an examination of media coverage of eDNA in Canada and the United States for the past approximately twenty years—likely a critical period in shaping understandings of and responses to eDNA. The findings indicate that eDNA is framed as a powerful tool, yet the social concerns that receive the most attention are those where there are financial interests at play, and these interests have to date eclipsed attending to relevant ethical considerations. Environmental DNA (eDNA) is an emerging technology used for understanding ecosystems, environmental change, and stressors. Cellular and extracellular DNA are collected from environmental samples instead of individual wildlife animals, and as such eDNA comes with associated logistical and ethical benefits. It is increasingly being used, yet to date public knowledge and perceptions of eDNA have not been explored. Given that most of the public gathers scientific information from news media sources, this is a logical first place to start. This paper reports on a framing and agenda-setting analysis of news media coverage of eDNA in Canada and the United States from 2000 to 2020. The findings indicate that eDNA is being framed as an emerging and powerful tool, although questions regarding its validity and reliability are raised vis-à-vis identifying the presence of invasive species. Less than half of the news articles analyzed address broader social or ethical issues in relation to eDNA, and the majority focus on the potential financial impacts of eDNA findings on development projects and business interests. The potential ethical advantages of non-lethal sampling methods used via eDNA sampling are not addressed, nor are the potential ethical issues raised by its potential use in bioprospecting, indicating that the current state of agenda setting regarding eDNA in these newspapers is focused on economic impacts, to the exclusion of potential ethical issues. This unfolding news coverage will likely be key to understanding public perceptions of this novel technology. [ABSTRACT FROM AUTHOR]