The problem raised by the potential influence of individuals’ specific interests on how well they conduct their missions, particularly within political bodies or public administration, has long been highlighted. However, the category of “conflict of interest” (COI) itself only emerged with its current meaning in the 1950s, gaining prominence in the biomedical sector in the 1980s, before becoming a widespread lens through which public health issues and scientific controversies are problematized. Based on a documentary analysis (official documents, press reviews, scientific publications), and for the more recent period on a series of interviews, this chapter offers a sociohistorical analysis of this trajectory. The objective is threefold: first, to explain the circulation of COI between different social spaces; second, to analyze the continuities and discontinuities in the actual use of this social category; and third, to reflect on the effects of these historical dynamics on its current social and political role. The chapter identifies and analyzes four historical phases: (1) the birth of COI in the US political domain, in a context marked by scandals around the military–industrial complex and the growing involvement of the state in the regulation of the economy; (2) the importation of this category into biomedical research, in response to controversies about academic entrepreneurship; (3) the international expansion of the category and the broadening of its use (to target the multi-layered production of corporate bias in biomedical science and regulation); and (4) the mediatization and politicization of COI issues in biomedicine from the mid-2000s.