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The stress phenomenon is illustrated and the impact of stress on the nervous system, neurodegenerative diseases, and mental disorders is examined. The connection between stress and the hippocampus - and its association with memory functions - is described. In particular, the pathophysiological significance of stress in Alzheimer's disease, multiple sclerosis, anxiety, depression, posttraumatic stress disorder, and schizophrenia is investigated.Stress plays a major role in various (patho)physiological processes associated with neurodegenerative diseases and mental disorders. In principle, stress has the potency to exert either ameliorating or detrimental effects. The specific outcome depends on multiple variables. However, the amount of stress experienced in relation to activated physiological processes that aim at successful coping and positive adjustments (i.e., stress response) most often is overwhelming - and may thus become detrimental in the long-term. Moreover, the hippocampus is sensitive to stress, and its involvement in neurodegeneration - in the course of stress-related disease processes - may account for severe clinical disabilities (e.g., memory loss).