The relationship between stress, depression, anxiety, and functional somatic disorders has been well documented, as well as their strongly negative interaction. A substantial body of research tries to link these conditions. These efforts have established several conceptual bridges that connect stress, psychological alterations, and coexistence of chronic disorders. The ‘fight-or-flight” response and the activation of the autonomic nervous system and hypothalamo-pituitary-adrenal (HPA) axis is the classical way to bring to the mind the behavioral and physiological response to the events assessed as threat. The paradoxical action, adaptation and damages of these mediators are already recognized. Sterling and Eyer recognized the function of the mediators as a body trial to maintain the disrupted homeostasis within the context of daily events (allostasis). The exact way of association of these conditions still stays incomplete. One new multi-disciplinary model based on the knowledge of physiology, psychiatry, pharmacology, and thermodynamics will show why: 1. the flight or fight response, from the aspect of the principles of homeostasis, has to be re-evaluated, 2. the physiological and behavioral responses of the stressful events are just adaptive. 3. the somatic disorders have to be seen as collateral damages, within the trial of the body to regain the homeostasis. 4. Appearance of the psychological/psychiatric responses is just ‘a part of the game”. Understanding the origin of the comorbidity is the way of finding the treatment, which in the optimal case adresses all of these diagnoses as a collective, rather than just looking at them separately.