A Reviews and Overviews article on validation of the diagnosis of posttraumatic stress disorder (PTSD) by North et al. (7) made me think about how an illness is the interaction between a cause and a reaction. Tumor, rubor, color, and dolor—the classic signs of inflammation—cause patients to seek treatment. These same signs help physicians identify a wide range of pathogenic causes, from acquired infection to inherited autoimmunity. North and colleagues argue that we need to conceptualize PTSD the same way. The significance of the causes, which range from the Holocaust to minor automobile accidents, can only be assessed in the context of the patients’ stress disorders, their reaction to the putative cause. As we approach DSM-V and we long for illnesses that have defined causes, like viruses or gene mutations, these authors remind us that we have much to learn by inquiring of our patients what distresses them. This conceptualization of PTSD encountered some resistance from the article’s reviewers, who pointed that this new approach to diagnosis could become circular: a disorder originally conceived as a reaction to a trauma now defines the trauma by the reaction. However, North and colleagues cogently present the case that we cannot assume that as psychiatrists we are able to divine independently what the pathological significance of events in their lives should be, without considering their reactions. They further point out that their approach mandates a new rigor in the diagnosis of PTSD, because careful symptomatic and biological assessment of the reaction and full understanding of the circumstances of the patient are necessary to pinpoint the cause.