This article aims at showing how “what is?” questions may open the way to move from our everyday acquaintance with what-is questions to a discussion of perennial philosophical issues, such as the relation between what is universal and individual, the relation between essence and appearance, as well as that between constancy and change. Add to this the initial prominence of thing concepts in Greek philosophy (embodied in the substance concept) and the eventual dominance of relational concepts (function concepts). This will be done by contrasting the distinctions employed with the impasse entailed in one-sided ismic orientations. Such an undertaking will have to account for both uniqueness and coherence. In addition, the distinction between conceptual knowledge and concept-transcending knowledge will serve the purpose of highlighting the limits of rational understanding as expressed in what-is questions as well as the unavoidability of the use of primitive terms. This, in turn, will require a brief account of the unavoidability of indefinability. It will be argued that what is needed is an integral and encompassing idea of the universe in its unity (coherence/relatedness) and diversity (uniqueness/irreducibility). The conclusion reached will underscore the necessity to avoid reductionism and to affirm both sides of above-mentioned coin: uniqueness and coherence. Therefore, to accomplish this goal such an encompassing perspective will have to deepen what-is questions by contemplating what-is-the-meaning-of? questions. Clearly, what-is? questions open an entrance to the basic distinctions implicit in philosophy as well as within the various academic disciplines – including the natural sciences and the humanities.

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