C. P. Snow’s famous Two Cultures essay has become a foil for decades of discussions over the relation between science and the humanities. The problem of the “two cultures” is often framed in terms of how the particular epistemological claims or general intellectual orientations of particular individuals on either side of this purported divide obstruct interdisciplinary dialogue or cooperation. This formulation, however, fails to consider the institutional frameworks within which such debates occur. This article examines the broader structural constraints that provide incentives, erect barriers, or otherwise shape the potential for interdisciplinary research and practice, with particular attention to work involving the life sciences. It argues that in order to understand the nature and scope of the problems facing interdisciplinary work, we must focus on the institutional constraints that shape how individuals frame questions, pursue investigations, develop careers, and collaborate.