Ketamine, a non-competitive NMDA glutamate receptor antagonist, is a multimodal anesthetic drug which has become increasingly popular in the treatment of pain following traumatic events. However, potential impacts of post-trauma ketamine administration on the development of neuropsychiatric disorders such as traumatic brain injury (TBI) symptoms and post-traumatic stress disorder (PTSD) remain controversial. To address these issues, previous studies have investigated the effects of ketamine injection on TBI and PTSD related biology and behaviors using laboratory animals. We also reported that a clinically relevant route of ketamine administration, an intravenous (IV) ketamine infusion, produced dose-dependent and sex-specific effects on analgesia, dissociative behaviors, fear memory, stress hormones, inflammatory cytokines, and in vivo brain energy utilization in male and female rats. Therefore, it is important to discuss translational ketamine research with a particular emphasis on the route, dosages, timing of ketamine administration as well as interaction between traumatic injury and ketamine. Finally, potential molecular and cellular mechanisms by which ketamine may impact neuropsychiatric disorders will be presented to improve translation between preclinical and clinical research on ketamine.