The purpose of this article is to encourage research investigating the role of measured gene-environment interaction (G x E) in the etiology of posttraumatic stress disorder (PTSD). PTSD is uniquely suited to the study of G x E as the diagnosis requires exposure to a potentially-traumatic life event. PTSD is also moderately heritable; however, the role of genetic factors in PTSD etiology has been largely neglected both by trauma researchers and psychiatric geneticists. First, we summarize evidence for genetic influences on PTSD from family, twin, and molecular genetic studies. Second, we discuss the key challenges in G x E studies of PTSD and offer practical strategies for addressing these challenges and for discovering replicable G x E for PTSD. Finally, we propose some promising new directions for PTSD G x E research. We suggest that G x E research in PTSD is essential to understanding vulnerability and resilience following exposure to a traumatic event.