Posttraumatic stress disorder (PTSD) is a debilitating condition that adversely affect mental and physical health. Recent studies have increasingly explored the role of the immune system in risk for PTSD and its related symptoms. Dysregulation of the immune system may lead to central nervous system tissue damage and impair learning and memory processes. Individuals with PTSD often have comorbid inflammatory or auto-immune disorders. Evidence shows associations between PTSD and multiple genes that are involved in immune-related or inflammatory pathways. In this review, we will summarize the evidence of immune dysregulation in PTSD, outlining the contributions of distinct cell types, genes, and biological pathways. We use the Human Leukocyte Antigen (HLA) locus to illustrate the contribution of genetic variation to function in different tissues that contribute to PTSD etiology, severity, and comorbidities.