Advocates of literary Darwinism, cognitive cultural studies, neuroaesthetics, digital humanities, and other such hybrid fields now seek explicitly to make the aims and methods of one or another humanities discipline approximate more closely the aims and methods of science, and at their most visionary, they urge as well the overall integration of the humanities and natural sciences. This essay indicates some major considerations—historical, conceptual, and pragmatic—that may be useful for assessing these efforts and predicting their future. Arguments promoting integration often involve dubious teleological models of intellectual history and betray limited understandings of the distinctive epistemic orientations and cultural functions of the humanities vis-à-vis the sciences. Recurrent institutional difficulties encountered by scholars and/or scientists in hybrid fields reflect steep prestige differentials between the humanities and sciences, along with significant differences of training, experience, style, and temperament. Meanwhile, both the sciences and humanities are being shaken up by technological and related intellectual developments. Though worrisome, the new disciplinary configurations are thus likely to play out in surprising and, not inconceivably, positive ways.