Posttraumatic stress disorder (PTSD) is a serious and debilitating condition with a prevalence rate of approximately 8% in the United States. Given the number of veterans returning from conflicts around the globe with PTSD, and the substantial number of civilians experiencing traumas, new perspectives on the biology of PTSD are needed. Based on the concept that PTSD is a disorder of stress response systems, numerous studies have suggested changes in hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenal-medullary (SAM) system function in patients with PTSD. Given that both glucocorticoids and catecholamines exert powerful effects on the immune system, it is surprising that relatively few studies have examined immune changes in patients with PTSD. Moreover, patients with PTSD are known to have increased rates of comorbidity with somatic disorders that involve immune and inflammatory processes. Patients with PTSD have been found to exhibit a number of immune changes including increased circulating inflammatory markers, increased reactivity to antigen skin tests, lower natural killer cell activity, and lower total T lymphocyte counts. Studies with humans and rodents suggest that certain proinflammatory cytokines are able to induce neurochemical and behavioral changes that resemble some key features of PTSD. This short article reviews immune alterations in PTSD, and considers possible mechanisms by which such changes may be related to neuroendocrine alterations and medical comorbidities of PTSD.