The stress response system, as vital mediator of the individual's health/illness dynamics at physical, psychological, and social levels, is modeled through a systems approach. This extremely complex self-regulating system involves multiple causal factors, nonlinearities, and time delays. Key basic functions are surveillance, mobilization of resources, feedback, and purpose. The underlying physiological stress response comprises three main mechanisms: autonomic nervous system, hormonal system, and immune response system. Their afferent pathways are presented in a flow diagram, and integrated into the full system which includes the psycho-social dimensions. The main features of this overall system comprise: psycho-social dynamics, feedback and feedforward monitors, self-concept, evaluation and strategy-decision making, generalized coping resources, mobilization of response strategies, and behavioral control. Stressors, as potential producers of stress, are illustrated in the physical, psychological, and social domains. A U-shaped universal dose-response curve is helpful in understanding stressor-destressor actions. Destressors are similarly considered, with special relation to lifestyle. Finally, the concept of eustress is developed as the ideal condition toward which this complex homeostatic system works.