The construct of allostasis is defined as change in the functioning of biological systems as a result of prolonged exposure to stress. In this article, the construct of bio-behavioral allostasis is proposed to describe peri-traumatic, shorter-term, and chronic changes in neurobiological systems and behaviors that account for the development and long-term maintenance of posttraumatic stress disorder (PTSD) symptoms and associated clinical features. The conceptual framework of bio-behavioral allostasis is applied to generate hypotheses about how premorbid vulnerabilities in different neurobiological systems interact with allostasis to predict heterogeneity in PTSD clinical profiles and patterns of comorbidity likely to develop after trauma exposure. The model offers a means by which to integrate independent theories of PTSD etiology to more fully account for unique features of PTSD, thereby improving its diagnostic discriminant validity. It also enables the identification of symptoms common across disorders that develop during exposure to adverse environments. Conceptualizing PTSD as a process of dynamic allostasis can advance our understanding of trauma-related diagnostic syndromes and inform the development of comprehensive treatments.