Introduction and Definition: Post-Traumatic Stress Disorder (PTSD) is a psychiatric condition arising from exposure to traumatic events. The World Health Organization (WHO) defines PTSD as: “a mental health condition that develops in some people who have experienced or witnessed a traumatic or frightening event such as a natural disaster, a serious accident or assault, a terrorist act or military combat, or those who have been threatened with death, sexual violence or injury”. The most common symptoms of PTSD include sleep disturbances, recurrent nightmares, and intense distress over reminders. The condition’s first recognition in the third edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-III) in 1980 revolutionized the clinical understanding of trauma's long-term psychological and physiological effects. Nowadays, PTSD’s relevance continues to grow in clinical neuroscience as research reveals how trauma reshapes the brain’s architecture and function. Body: This encyclopedia entry explores the neurobiology of PTSD, beginning with an overview of its diagnostic criteria under DSM-5, which include symptoms across four clusters: intrusion, avoidance, negative alterations in cognition and mood, and hyperarousal. The entry focuses on several key brain regions consistently implicated in PTSD. The amygdala becomes hyperactive, which is associated with excessive threat detection and fear responses. The hippocampus often exhibits reduced volume, contributing to impaired memory processing and difficulties in distinguishing safe contexts from traumatic memories. The prefrontal cortex (PFC) shows reduced activity, limiting top-down emotional regulation and exacerbating reactivity. These alterations are further compounded by dysregulation in the Hypothalamic-Pituitary-Adrenal (HPA) axis, which affects cortisol levels and perpetuates chronic physiological stress. Neuroimaging and structural imaging studies confirm these findings, while research into developmental trauma highlights how early adversity affects brain maturation. The entry also explores how these insights inform treatment, including CBT and pharmacological approaches. Future directions include examining the environmental, genetic, and epigenetic factors that support resilience to trauma, as well as developing novel interventions such as psychedelic-assisted therapy and decoded neurofeedback therapy.