This article discusses a number of key issues in the history of sixteenth-century Iberian science: the role of sixteenth-century Spanish science in the construction of modern science; the encounter of Western science with other forms of knowledge; the relationship between science and empire; and the construction of a Eurocentric world order. The author concludes by suggesting that the idea of “comprehension” -as both a form of appropriation and a process of self-construction- can help explain the political character of science and its role in the Iberian conquest of the New World.