Ego-Self alienation stands as one of the most consequential diagnostic categories in depth-psychological literature, denoting the condition in which the vital axis connecting the ego to its transpersonal ground — the Self — is ruptured or chronically impaired. Edward Edinger, whose *Ego and Archetype* (1972) remains the locus classicus of this formulation, distinguishes two poles of dysfunction: inflation, in which the ego remains unconsciously identified with the Self and arrogates to itself divine attributes, and alienation proper, in which that identification collapses catastrophically, leaving the ego severed from its source of meaning, acceptance, and ontological legitimacy. Alienation, on Edinger’s account, originates developmentally when parental rejection is registered as rejection by the divine — the Self — thereby inscribing a permanent wound in the psyche. Karen Horney approaches cognate territory from a different angle: her ‘alienation from self’ names the neurotic abandonment of one’s ‘real self’ under the compulsive demands of the idealized image, producing depersonalization, affective deadening, and a pervasive inability to assume responsibility. Samuels and the Developmental School locate the mechanism in the early parent-child dyad, following Neumann’s claim that the mother initially carries the child’s Self. Gnostic parallels, invoked by both Edinger and King, illuminate the archetypal grammar underlying the concept: cosmic alienation as the condition of the divine spark imprisoned in matter. Across these traditions, ego-Self alienation is understood not merely as personal psychopathology but as a civilizational and spiritual crisis of modernity.