This article seeks to determine whether the concept of meaning is relevant in hard sciences and, if so, under which of the four semiotic regimes that are now firmly established in the field of interactional research . The study starts with the one whose main feature is insignificance. Called programming, it best accounts for the scientific epistemology according to which, during ages, scientists refrained from attributing the least signification to the regularities (and corresponding “laws”) that sciences were discovering. The opposite stance, focussing on unpredictability, leads to another semiotic vacuum, nonsense. All interpretations of reality as a produce of pure chance fall under this regime of assent to the accidental. After a brief survey of these options, we concentrate on the remarkable illustrations that contemporary sciences, via their most advanced postulates (incompleteness, complexity, emergence), provide in terms of manipulation and adjustment, two regimes which entail positive modes of significance but are much more risky as heuristic devices.