PTSD is responsive to treatment with selective serotonin reuptake inhibitors, but response rates rarely exceed 60%, and even fewer patients (20%-30%) experience improvement that could be characterized as remission. Thus, there is a clear need to develop novel and improved therapeutics for PTSD. A growing body of preclinical evidence suggests that activation of the Substance P (SP) and its receptor NK1 is anxiogenic and that NK1 antagonists, upon chronic administration, exert significant dampening (albeit complex) effects on the SP-NP system. Furthermore, several stress paradigms are believed to exert many of their deleterious effects on hippocampal structures via enhancement of SP-NK1 system. Overall, excess activity of the SP-NK1 system stands as a prime candidate for involvement in the pathophysiology of anxiety disorders such as PTSD.