The One Health concept has inspired a rich vein of applied research and scholarly reflection over the past decade, yet with little influence from qualitative methodologists. With this overview, we describe the underpinning assumptions, purposes, and potential pitfalls of data collection techniques and methods of data analysis in key qualitative research methodologies. Our aim is to enhance One Health collaborations involving qualitative researchers, veterinary epidemiologists, and veterinary economists. There exist several distinct traditions of qualitative research, from which we draw selectively for illustrative purposes. Notwithstanding important distinctions, we emphasize commonalities and the potential for collaborative impact. The most important commonality is a shared focus on contextualizing human behavior and experience–culturally, economically, historically, and socially. We demonstrate that in-depth attention to context can assist veterinary economists and epidemiologists in drawing lessons from the implementation of policies and programs. In other words, qualitative researchers can assist One Health teams in distilling insights from “success stories,” but also from adverse events and unintended consequences. As a result, qualitative researchers can contribute to One Health research and policy discussions by formulating more accurate and contextually-relevant parameters for future quantitative studies. When performed well, qualitative methodologies can help veterinary economists and epidemiologists to develop impactful research questions, to create more accurate and contextually-relevant parameters for quantitative studies, and to develop policy recommendations and interventions that are attuned to the political and socio-cultural context of their implementation. In sketching out the properties and features of influential methodologies, we underscore the value of working with seasoned qualitative researchers to incorporate questions about “what,” “how,” and “why” in mixed-methods research designs.