In this chapter I introduce the research program of evolutionary medicine (EM) and present mismatch theory as a part of it. Only in the second chapter will I begin to zoom in on the concept of mismatch in particular. My primary goal in this chapter is to explain what evolutionary medicine is about (2.1) and to present the six causes for our vulnerability that EM provides, while also highlighting points of contact with debates taking place in biomedical ethics (2.2). After a summary of the application of the concepts of nature and disease within EM (2.3), I will outline the reasons for which evolutionary biology and medicine have become divided, and how these reasons still pose the main challenges to the unifying aspirations of the research program of EM (2.4). Through this analysis it will become apparent why mismatch theory is a central anchor point for the debates surrounding the complicated relationship between evolutionary theory, medical practice and biomedical ethics, and why the concept is in need for a more refined analysis.