The colonization of America implied the integration of the Indigenous people to a new political entity, the Spanish Empire. Attributing a legal status to those populations constituted a major political issue, a question of which all the historical actors were fully aware. Consequently, the definition of the legal condition of the Indians mobilized different social sectors and generated intense debates, closely related to the interests at stake. In this conflictive context, the Spanish Crown had to take a position. Drawing on a series of recent studies that examine the question from the perspective of the history of ideas, power, and institutions, the present article will focus on the process which led the Spanish Crown to attribute to the Indigenous people the status of personae miserabiles.