The authors provide a detailed review of the extant gene–environment interaction (GxE) research in the etiology of posttraumatic stress disorder (PTSD). They begin with a discussion of why PTSD is uniquely fitting for the innovative framework of GxE methodology, followed by a review of the heritability and main effect molecular genetics studies of PTSD. Next, they discuss the six GxE investigations to date on PTSD. They end with a discussion of future directions and significance of this research, with an emphasis on the expansion of psychosocial factors that may be fitting environmental variables for inclusion in this new research area. The authors posit that GxE research is vital to elucidating risk and resilience following exposure to a potentially traumatic event.