Homeostasis, a self-regulating process that aims for stability, is presented to be the most fundamental regulatory principle of the psyche. Stability, or avoiding the extremes, is crucial for survival. The mind operates on different layers of homeostasis. Freud's three phylogenetic layers and regulating principles, namely nirvana, constancy, and psychic structure, are reviewed here. The self-image and its identity of perception form the core of the structure. In a clinical context, a cure that deviates too much from the self-image is perceived as threatening stability. The therapeutic relationship is an ideal setting for fostering the ego's mentalization capacity and the development of psychic structure. This paper demonstrates how mentalization and autonomous self-regulation challenge pathologic homeostatic regulation through clinical examples. The defensive resistance to cure, with its intriguing deep unconscious phylogenetic roots in homeostatic regulation, underscores the practical implications of these theoretical viewpoints in a clinical setting.