Posttraumatic stress disorder (PTSD) now sits within the newly created “Trauma- and Stressor-Related Disorders” section of the Diagnostic and Statistical Manual of Mental Disorders (fifth edition; DSM-5). Through the refinement and expansion of diagnostic criteria, the DSM-5 version better clarifies the broad and pervasive effects of trauma on functioning, as well as the impact of development on trauma reactions. Aggressive and dissociative symptoms are more thoroughly characterized, reflecting increasing evidence that reactions to trauma often reach beyond the domains of fear and anxiety (these latter domains were emphasized in DSM-IV). These revised criteria are supported by decades of preclinical and clinical research quantifying traumatic stress–induced changes in neurobiological and behavioral function. Several features of the DSM-5 PTSD criteria are similarly and consistently represented in preclinical animal models and humans following exposure to extreme stress. In rodent models, for example, increases in anxiety-like, helplessness, or aggressive behavior, along with disruptions in circadian/neurovegetative function, are typically induced by severe, inescapable, and uncontrollable stress. These abnormalities are prominent features of PTSD and can help us in understanding the pathophysiology of this and other stress-associated psychiatric disorders. In this article we examine some of the changes to the diagnostic criteria of PTSD in the context of trauma-related neurobiological dysfunction, and discuss implications for how preclinical data can be useful in current and future clinical conceptualizations of trauma and trauma-related psychiatric disorders.