This review summarizes the current understanding of the biological mechanisms underlying posttraumatic stress disorder (PTSD). PTSD is a mental disorder caused by exposure to traumatic events, characterized by intrusive memories, avoidance, emotional numbing, and hyperarousal. While initially viewed as a psychological condition, recent research has revealed significant biological underpinnings, including psychophysiological, structural, and functional neuroimaging, endocrinological, genetic, and molecular biological findings in both humans and animal models. Psychophysiological studies have shown heightened autonomic and facial reactivity to trauma-related stimuli in PTSD patients, as well as exaggerated startle responses. These findings suggest that PTSD is associated with increased sensitivity to threat and may be linked to pre-existing vulnerabilities or acquired changes in the nervous system. Psychophysiological markers, such as heart rate, skin conductance, and ERP responses, are useful in predicting PTSD risk and assessing treatment outcomes. Structural neuroimaging studies have identified reduced hippocampal volume in PTSD patients, which may be a pre-trauma risk factor or an acquired feature of the disorder. The prefrontal cortex, particularly the ventromedial prefrontal cortex (vmPFC), also shows volume reductions, which may contribute to impaired fear inhibition and emotional regulation. Functional neuroimaging studies have shown altered activity in the amygdala, vmPFC, and dACC, with the amygdala showing exaggerated activation in response to trauma-related stimuli. Neuroendocrinological studies have revealed abnormalities in catecholamines, cortisol, and other hormones, suggesting that PTSD may involve dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. The serotonin system is also implicated in both the acute mediation of PTSD symptoms and the modulation of PTSD risk. Neuropeptide Y (NPY) has protective effects during stress, and lower levels are associated with increased PTSD symptoms. Genetic studies suggest that genetic factors account for a significant portion of vulnerability to PTSD, with some genes involved in dopamine, serotonin, and HPA axis regulation. Epigenetic mechanisms, such as DNA methylation and histone deacetylation, may also play a role in PTSD pathogenesis. These findings highlight the complex interplay between genetic, environmental, and neurobiological factors in the development and maintenance of PTSD. Understanding these mechanisms is crucial for developing effective treatments and interventions for this disorder.This review summarizes the current understanding of the biological mechanisms underlying posttraumatic stress disorder (PTSD). PTSD is a mental disorder caused by exposure to traumatic events, characterized by intrusive memories, avoidance, emotional numbing, and hyperarousal. While initially viewed as a psychological condition, recent research has revealed significant biological underpinnings, including psychophysiological, structural, and functional neuroimaging, endocrinological, genetic, and molecular biological findings in both humans and animal models. Psychophysiological studies have shown heightened autonomic and facial reactivity to trauma-related stimuli in PTSD patients, as well as exaggerated startle responses. These findings suggest that PTSD is associated with increased sensitivity to threat and may be linked to pre-existing vulnerabilities or acquired changes in the nervous system. Psychophysiological markers, such as heart rate, skin conductance, and ERP responses, are useful in predicting PTSD risk and assessing treatment outcomes. Structural neuroimaging studies have identified reduced hippocampal volume in PTSD patients, which may be a pre-trauma risk factor or an acquired feature of the disorder. The prefrontal cortex, particularly the ventromedial prefrontal cortex (vmPFC), also shows volume reductions, which may contribute to impaired fear inhibition and emotional regulation. Functional neuroimaging studies have shown altered activity in the amygdala, vmPFC, and dACC, with the amygdala showing exaggerated activation in response to trauma-related stimuli. Neuroendocrinological studies have revealed abnormalities in catecholamines, cortisol, and other hormones, suggesting that PTSD may involve dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. The serotonin system is also implicated in both the acute mediation of PTSD symptoms and the modulation of PTSD risk. Neuropeptide Y (NPY) has protective effects during stress, and lower levels are associated with increased PTSD symptoms. Genetic studies suggest that genetic factors account for a significant portion of vulnerability to PTSD, with some genes involved in dopamine, serotonin, and HPA axis regulation. Epigenetic mechanisms, such as DNA methylation and histone deacetylation, may also play a role in PTSD pathogenesis. These findings highlight the complex interplay between genetic, environmental, and neurobiological factors in the development and maintenance of PTSD. Understanding these mechanisms is crucial for developing effective treatments and interventions for this disorder.