Although stress responses initially evolved as adaptive processes, prolonged stress may severely affect mood, well-being, behavior, and health. The stress response is orchestrated by the body's core stress system, in part via the release of glucocorticoids from the adrenal glands, resulting in the coordination of a number of physiological responses aimed at preparing the body to respond to an imminent threat. Based on the nature and timing of the stressor, severe stress can have dramatic effects on health, from altering the body's homeostasis to triggering or aggravating numerous diseases.

The brain has many non-uniformly distributed receptors to stress hormones (glucocorticosteroids and mineralocorticoids), making it particularly vulnerable to stress. As a result, chronic stress can lead to structural changes throughout the brain, including atrophy, a decreased number of neurons, lower rates of neurogenesis in the hippocampus, and decreased neuronal branching. The hippocampus, which has the highest density of glucocorticosteroid receptors in the brain, is particularly vulnerable to stress. In consequence, high concentrations of stress hormones can cause declarative memory disorders and weakened verbal memory, as well as disrupted cognitive function and judgement. In genetically vulnerable individuals, the compounded effects of stress can also trigger psychiatric disorders, such as psychosis or depression. In all cases, the health effects of stress depend heavily on the individual and timing of the exposure.

Stress modifies the release of hormones that play a critical role in the immune system, and many stress hormones also directly act on tissues of the immune system. Stress can particularly impact the immune system by reducing the activity of phagocytes and lymphocytes, facilitating the growth of malignant cells, genetic instability, and cancer progression, alongside increasing the body's vulnerability to a number of other diseases.

In parallel, stress also stimulates the sympathetic nervous system, initially leading to an increased heart rate. Thereafter, stress can increase blood pressure, blood lipid levels, and blood clotting, all of which may heighten the risk of cardiac arrhythmias and myocardial infarction. On top of this, stress tends to trigger behaviors that are detrimental to cardiovascular health, such as smoking.

The gastrointestinal system similarly is affected by stress, both directly and indirectly. Indeed, stimulation of the sympathetic nervous system by stress directly affects the gastrointestinal-specific nervous system (the myenteric plexus), potentially leading to gastrointestinal movement disorders and altered rates and extent of gastrointestinal secretions. Stress may also reduce blood flow to the gastrointestinal tract and increase intestinal bacteria counts.

Chronic stress can negatively impact sexual behaviors and heighten the risk of infection in male reproductive organs. It can also affect the menstrual cycle, leading to, heavier, more painful periods, and/or magnifying the physical symptoms of menopause.

Finally, stress and the endocrine system are closely related, mutually influencing each other's activity. Even minimal stress can activate the main hypothalamic-pituitary-adrenal stress axis, which is extensively linked to several hormone secreting systems.

Stress management strategies may include regular physical activity; practicing relaxation techniques, such as deep breathing, meditation, yoga, tai chi or massage; and spending time with family and friends and doing hobbies, such as reading a book or listening to music.