The aim of this essay is to elaborate philosophical and ethical underpinnings of posthumous diagnosis of famous historical figures based on literary and artistic products, or commonly called retrospective diagnosis. It discusses ontological and epistemic challenges raised in the humanities and social sciences, and attempts to systematically reply to their criticisms from the viewpoint of clinical medicine, philosophy of medicine, particularly the ontology of disease and the epistemology of diagnosis, and medical ethics. The ontological challenge focuses on the doubt about (...) the persistence of a disease over historical time, whereas the epistemic challenge disputes the inaccessibility of scientific verification of a diagnosis in the past. I argue that the critics are in error in conflating the taxonomy of disease and the act of diagnosing a patient. Medical diagnosis is fundamentally a hypothesis-construction and an explanatory device that can be generated under various degrees of uncertainty and limited amount of information. It is not an apodictic judgment as the critics presuppose, but a probabilistic judgment with varying degrees of plausibility under uncertainty. In order to avoid this confusion, I propose that retrospective diagnosis of a historical figure be syndromic without identifying underlying disease, unless there is justifiable reason for such specification. Moreover it should be evaluated not only from the viewpoint of medical science but also in a larger context of the scholarship of the humanities and social sciences by its overall plausibility and consistency. On the other hand, I will endorse their concerns regarding the ethics and professionalism of retrospective diagnosis, and call for the need for situating such a diagnosis in an interdisciplinary scope and the context of the scholarship of the historical figure. I will then enumerate several important caveats for interdisciplinary retrospective diagnosis using an example of the retrospective diagnosis of Socrates for his life-long intermittent neurologic symptoms. Finally, I will situate the present argument in a larger context of the major debate among the historians of medicine and paleopathologists, and discuss the similarities and differences. (shrink)