Scientific disciplines are distinct not only in what they know but in how they know what they know—that is, in their “epistemic cultures.” There is a close relationship between the technologies that a field utilizes and sanctions and the process of inquiry, the character and meaning of corroborative data and evidence, and the kinds of models and theories developed in a field. As the machinery changes, epistemic practices also change. A case in point is how the epistemic practices of historians are reconfigured by the introduction of Geographic Information Systems (GIS). We argue that GIS mediates historical understanding and knowledge creation in at least three ways: (a) by allowing historians to bring new sets of data into analysis, (b) by introducing novel questions, fresh insights, and new modes of analysis and reasoning, or discovering new answers to older questions; and (c) by providing new tools for historians to communicate with each other and with their audiences. We illustrate these mediations through the study of the historiography of Budapest Ghettos during World War II. Our study shows how GIS functionalities reveal hitherto unknown aspects of social life in the ghettos, while pushing certain other aspects into the background.