Opinion Statement:Purpose In this article, we present data incorporating heart rate variability (HRV) into a graded virtual reality protocol performed in both a combat environment and an active control (classroom) environment, for combat Veterans with and without PTSD.Recent Findings Exposure therapy for PTSD has proven effective. There is increasing interest in the use of virtual reality exposure therapy (VRET)-customized environments incorporating auditory, visual, and olfactory sensory modalities, to augment exposure-based treatment for PTSD. Particularly for combat Veterans, VRET may offer the advantage of a more realistic in vivo exposure for treatment. When combined with concurrent psychophysiological data, VRET has the potential to inform PTSD diagnosis, predict therapeutic responsiveness, and provide objective indicators of treatment response. HRV was not different between Veteran with and without PTSD, but our group recently found that Veterans with PTSD had differential skin conductance responses compared with Veterans without PTSD.Summary Virtual reality is a promising treatment for PTSD. Methodological factors may have influenced the absence of significant findings in the current data. Future research which optimizes the potential use of psychophysiological assessments for the development of biomarkers and prediction of PTSD treatment response, or to inform the process of PTSD treatment, remain important.