Today's life rhythms and demands are often challenging and require intense physical and psychological efforts to be sustained. An individual reacts to the physical and mental strain that is potentially health-threatening by activating interconnected neuroendocrine circuits. This response allows the body to face and deal with the challenge and re-establish homeostatic equilibrium. If the individual perceives a noxious stimulus as too intense or its duration as too long, he may fail to cope with it, and incur maladaptation. In this case, the stress response does not resolve into a state of balance (either similar or new, i.e., adapted, compared with the state before stress hits), neuroendocrine parameters remain altered, and illness may ensue.

It is clear that stress has both a physical (objective) and a psychological (subjective) component: the latter, as described by Koolhaas and colleagues, depends on the individual perception of its predictability and controllability. The way a person can anticipate a certain stressor and then control it, largely defines the resulting stress response, how promptly and efficiently it is activated promoting adaptation, and how fast it is turned off once equilibrium has been recovered.

The time course of the stress response, characterized by measurable neuroendocrine and behavioral indexes, thus reveals whether a destabilizing stimulus is manageable, or conversely, cannot be handled and consequently becomes harmful.

This implies that not all stimuli that elicit strong neuroendocrine responses are real stressors, but only those that exceed the individual's ability to change and adapt.