Scientific literature is reviewed supporting a “consequence of war syndrome (CWS)” in Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn soldiers. CWS constituents include chronic pain and insomnia, other physical complaints, posttraumatic stress disorder (PTSD), anxiety, depression, and neuropsychological deficits. The foundation of CWS lies with the chronic stressors inherent to deployment and the cascade of biological events mediated and maintained by hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Such dysregulation is modified by the individual’s specific experiences at war, difficulty reintegrating to post-deployment life, and the onset or exacerbation of the chronic and comorbid physical, emotional, and cognitive disorders. The circuit network between the prefrontal cortex (PFC), amygdala, and hippocampus is particularly sensitive to the consequences of war. The review’s specific conclusions are as follows: HPA axis dysregulation contributes to the chronic insomnia and hyperarousal seen in soldiers. There is considerable symptom overlap between PTSD and blast-related head injury, and it is difficult to determine the relative contributions of the two disorders to abnormal imaging studies. In some cases, traumatic brain injury (TBI) may directly precipitate PTSD symptoms. While not intuitive, the relationship between TBI and postconcussion syndrome appears indirect and mediated through PTSD. Blast-related or conventional head injury may have little long-term impact on neuropsychological functioning; contrarily, PTSD particularly accounts for current cognitive deficits. The psychological experience of CWS includes a “war-within” where soldiers continue to battle an internalized enemy. Successful treatment of CWS entails transdisciplinary care that addresses each of the constituent disorders.© The Author(s) 2019.