Life events and severe adversities affect the brain and could elicit a significant stress response, resulting in adaptation or somatic and mental diseases. Severity, intensity, duration of the event, individual cognitive appraisal and emotional arousal, phase of the vital cycle, support, and resilience mediate the stress response. The purpose of the stress response is adaptation in front of challenges. Life events impact on a complex central neural network brainstem, hypothalamus, pituitary, limbic system with amygdala, with neurotransmitter alterations and circuits dysfunctions, especially serotoninergic, dopaminergic, noradrenergic and GABAergic, epigenetic changes and modification of gene expression. These are the biological substrates of highly prevalent stress-dependent cases of psychiatric disorders such as major depression, bipolar episodes, psychotic reactions, and anxiety disorders, as well as post-traumatic stress disorders. There is also a cascade from the brain to the peripheral body systems, such as the autonomic, the neuroendocrine and peptidergic, the musculo-skeletal, and the immune-inflammatory. These are the mechanisms of mediation between life events and somatic diseases and psychosomatic disorders. Thus, CNS and the body react to life events according to individual characteristics and personal history, with a real “biochemical storm.” The “lived experience” during life stress is a matter of brain and body changes.