So how should we interpret the comorbidity of posttraumatic stress disorder (PTSD), major depressive disorder, generalized anxiety disorder, mild traumatic brain injury, and alcohol use disorder identified in the DSM-5 field trials—with the highest reliability among those disorders for PTSD? In the routine clinical practice field trial settings, clinicians identified a spectrum of related disorders that may well have common genetic and environmental exposure vulnerabilities, but with a central tendency for PTSD to be the dominant clinical presentation in Veterans Affairs health care settings. Given the heterogeneity of PTSD with or without one or more of these comorbid presentations, the clinical course and response to treatment may well be “moderated” by these comorbidities (7). In this regard, the Institute of Medicine study notwithstanding, and as attested by several clinical practice guidelines (8), the PTSD diagnosis does predict a favorable response to a number of treatments, in addition to prolonged exposure therapy. Finally, brain imaging and other laboratory tests are emerging to add to the list of potential moderators that will predict differential response to treatment, but we have not yet reached a point where a biomarker will qualify as a diagnostic criterion for PTSD or any other DSM-5 disorder.