This paper is concerned with how best to think about the interface between psychoanalysis and disciplines and methodologies such as neuroscience and systematic empirical research which diverge so significantly from psychoanalysis both in terms of their theories of knowledge and their implicit or explicit views of the mental and of subjectivity. It is suggested that there is often a covert, untheorized scientism in neuropsychoanalytic and empiricist prescriptions for the reform and rescue of psychoanalysis, and that the reductionism underlying such arguments misunderstands and misrepresents the true nature of psychoanalytic discourse and practice. When important questions of epistemology are avoided, practical questions of method and pluralism are confused with essential orienting philosophical questions having to do with the nature of psychoanalytic knowledge. This often allows advocates for the epistemologically incautious merging of disciplines to excuse themselves from responsibility for justifying underlying principles and assumptions, which undermines the intellectual seriousness of psychoanalysis as a discipline. If accepted, it also makes it virtually certain that the empiricist or biologistic view will gradually replace psychoanalytic constructs with terms and categories, derived from research, which are valued first of all for their utility and measurability. The paper argues instead that, while there is value in the empirical wish to stand apart or gain distance from, in the end a hermeneutic and non-objectivist view is essential to psychoanalysis both as an orienting and a concluding framework. Moreover, the empiricist view is an imminent danger if not overseen by a constraining and integrative hermeneutic which can then address other disciplines with an appropriate combination of openness and critical attention. Lacking this, psychoanalysis risks being colonized by antithetical epistemologies under the guise of salutary prescriptions for integration and pluralism, which will lead inevitably to it becoming something other than itself.