Chronic stress is the physiological or psychological response induced by a long-term internal or external stressor. The stressor, either physically present or recollected, will produce the same effect and trigger a chronic stress response. There is a wide range of chronic stressors, but most entail relatively prolonged problems, conflicts and threats that people encounter on a daily basis. Several chronic stressors have been identified as associated with disease and mortality including "neighbourhood environment, financial strain, interpersonal stress, work stress and caregiving."

Stress responses, such as the fight or flight response, are fundamental. The complexity of the environment means that it is constantly changing. To navigate the surroundings, we, therefore, need a system that is capable of responding to perceived threatening and harmful situations. The stress response system thus has its role as an adaptive process to restore homeostasis in the body by actively making changes. For instance, the body will involve in an endocrine system response in which corticosteroids are released. This process is known as allostasis, first proposed by Sterling and Eyer (1988). Research has provided considerable evidence to illustrate the stress response as a short-term adaptive system. The immediate effects of stress hormones are beneficial in a particular short-term situation. The system is arguably a protective defense against threats and usually does not pose a health risk.

However, the problem arises when there is a persistent threat. First-time exposure to a stressor will trigger an acute stress response in the body; however, repeated and continuous exposure causes the stressor to become chronic. McEwen and Stellar (1993) argued there is a "hidden cost of chronic stress to the body over long time periods". That is often known as allostatic load. Chronic stress can cause the allostasis system to overstimulate in response to the persistent threat. And such overstimulation can lead to an adverse impact. To illustrate, the long-term exposure to stress creates a high level of these hormones. This may lead to high blood pressure (and subsequently heart disease), damage to muscle tissue, inhibition of growth, and damage to mental health. Chronic stress also relates directly to the functionality and structure of the nervous system, thereby influencing affective and physiological responses to stress. These subsequently can result in damage to the body.

Hans Selye (1907–1982), known as the "father of stress", is credited with first studying and identifying stress. He studied stress effects by subjecting lab mice to various physical, antigenic, and environmental stressors, including excessive exercise, starvation, and extreme temperatures. He determined that regardless of the type of stress, the mice exhibited similar physical effects, including thymus gland deterioration and the development of ulcers. Selye then developed his theory of general adaptive syndrome (GAS) in 1936, known today as "stress response". He concluded that humans exposed to prolonged stress could also experience hormonal system breakdown and subsequently develop conditions such as heart disease and elevated blood pressure. Selye considered these conditions to be "diseases of adaptation", or the effects of chronic stress caused by heightened hormonal and chemical levels. His research on acute and chronic stress responses introduced stress to the medical field.

Animals exposed to distressing events over which they have no control respond by releasing corticosteroids. The sympathetic branch of the nervous system is activated, also releasing epinephrine and norepinephrine.

Stress has a role in humans as a method of reacting to difficult and possibly dangerous situations. The "fight or flight" response when one perceives a threat helps the body exert energy to fight or run away to live another day. This response is noticeable when the adrenal glands release epinephrine, causing the blood vessels to constrict and heart rate to increase. In addition, cortisol is another hormone that is released under stress and its purpose is to raise the glucose level in the blood. Glucose is the main energy source for human cells and its increase during time of stress is for the purpose of having energy readily available for over active cells.

Chronic stress is also known to be associated with an accelerated loss of telomeres in most but not all studies.

Different types of stressors, the timing (duration) of the stressors, and genetic inherited personal characteristics all influence the response of the hypothalamic–pituitary–adrenal axis to stressful situations. The hypothalamic–pituitary–thyroid axis and other endocrine axes are also involved in the stress response. Those with a wealthy background have a stronger response to stress than those in the lower strata.^{[citation needed]}