Collaboration between anthropology and epidemiology has a long and tumultuous history. Based on empirical examples, this paper describes a number of epistemological lessons we have learned through our experience of cross disciplinary collaboration. Although critical of both mainstream epidemiology and medical anthropology, our analysis focuses on the implications of addressing each discipline's main epistemological differences, while addressing the goal of adopting a broader social approach to health improvement. We believe it is important to push the boundaries of research collaborations from the more standard forms of "multidisciplinarity," to the adoption of theoretically imbued "interdisciplinarity." The more we challenge epistemological limitations and modify ways of knowing, the more we will be able to provide in-depth explanations for the emergence of disease-patterns and thus, to problem-solve. In our experience, both institutional support and the adoption of a relativistic attitude are necessary conditions for sustained theoretical interdisciplinarity. Until researchers acknowledge that methodology is merely a human-designed tool to interpret reality, unnecessary methodological hyper-specialization will continue to alienate one field of knowledge from the other.