Post-traumatic stress disorder (PTSD) is a debilitating condition that only occurs in the aftermath of traumatic event exposure and is characterized by an impaired stress response and chronic, low-grade inflammation. Dysregulation of the immune system may contribute towards central nervous system tissue damage and exacerbation of fear memories following trauma. Patients with PTSD often have comorbid psychiatric and somatic disorders that are of themselves associated with heightened inflammation. Several immune-related genes have been associated with PTSD and other co-occurring disorders. In this review, we propose that chronic inflammation, particularly neuroinflammation, is an important contributory factor towards PTSD comorbidity. Thus, novel treatments that target dysregulated inflammatory processes could provide symptomatic relief from PTSD and its comorbid disorders. This review investigates the intricate links between chronic stress, anxiety and neuroinflammation and the potential impact of increased neuroinflammation on PTSD pathology and comorbidity.