The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for post-traumatic stress disorder (PTSD) consist of over twenty possible symptoms that can be divided into six broad categories. These categories correlate with specific brain networks that regulate emotions, behaviors, and autonomic function. Normal functioning of these networks depends on two key regions; the prefrontal cortex and the amygdala. The prefrontal cortex provides top-down executive control over amygdala, whereas the amygdala is critical for threat detection and activation of the ‘fight or flight’ response. Events that trigger extreme and/or prolonged fear can cause persisting dysregulation within the prefrontal-amygdala circuit; resulting in PTSD symptomatology. Studies indicate that effective treatment of PTSD, either psychotherapy or medications, reverses this prefrontal-amygdala dysregulation. This review article summarizes current knowledge and theories available in the medical literature from NCBI’s PubMed database regarding the underlying brain networks involved in PTSD.