This chapter summarizes the common neurobiological pathways underpinning the wide range of symptoms seen in trauma-related disorders and provides helpful language for psychoeducation that can instill hope in the brain’s capacity to heal. This chapter reviews the triune brain model and highlights the role of more primitive brain areas in carrying out automatic defensive responses to threat, as conceptualized in the defense cascade model. Particular attention is given to dissociative responses, including freezing and collapsing/playing dead. The authors highlight crucial brain areas such as the periaqueductal gray matter, which enacts these defenses in the body. The authors also discuss how sensory processing abnormalities in areas such as the vestibular system, the cerebellum, and the temporal lobe can explain psychotic-like and dissociative symptoms, which are frequently misinterpreted as psychosis or malingering. Finally, the chapter reviews intrinsic connectivity networks and difficulties with higher-order cognitive functions.