The work presents an extensive review on the theme of the crisis of meaning generated by uncertainty. Generally, uncertainty is considered an affective-cognitive condition of human experience that is characterized by a crisis of predictability of the expected future, of decision-making, of identity, of sociability, and of agency. Uncertainty requires an intense effort of sensemaking to re-establish a worldview as ordered and predictable. On the one hand, uncertainty is a natural condition of human experience, on the other hand it is the exceptional condition of discontinuity/rupture/turning point generated by the breaking of common sense, of the habits of daily life and by the crisis of the frames of meaning of the worldview. A broad and varied set of perspectives from the interdisciplinary fields of anthropology, philosophy, semiotics, narrative studies, cognitive and social psychology, cultural psychology and psychoanalysis are considered. The authors discuss a series of defensive processes, control recovery strategies, meaning making processes for the re-establishment of an orderly vision of the world, of one's own identity and one's own social systems of belonging. Finally, uncertainty as a condition of decoupling with one's own world is therefore the condition that makes possible the transformation, development and generation of new semiotic systems of relationship by means of sensemaking processes. This is followed by a reflection aimed at enhancing the ability to sustain uncertainty, to contain and to elaborate it, and to enhance the reflective capacity against the thrust of its denial, the thrust of its elimination through totalizing, saturated, rigid and extensive defensive strategies.