Kendler’s chapter provides a compelling account of how little evolved important premises of twentieth- and twenty-first-century psychopathology concepts represented in the Diagnostic and Statistical Manuals (DSMs) are from frameworks developed in earlier centuries that came to the fore in the nineteenth century, emphasizing a categorical distinction between cognition and emotion in characterizing broad classes of disorders. He then poses questions about how the recent NIMH Research Domain Criteria (RDoC) initiative relates to that heritage. The present commentary similarly places RDoC in that tradition yet differentiates RDoC from the DSMs. By design, RDoC is nonreductionistic and initially much less comprehensive and much more research based, largely confining its substantive elements to intersections of well-developed psychological constructs (important in but not confined to) psychopathology with well-developed psychological and biological data. As such, RDoC is much better positioned to support and drive recently growing interest in computational psychiatry.