This chapter outlines the role of pharmacological therapies in managing PTSD, emphasizing the roles of the non-classical psychedelics, 3,4-methylenedioxymethamphetamine (MDMA) and ketamine. These drugs ameliorate core PTSD symptoms, but require vigilant clinical oversight. Other drugs that alleviate core PTSD symptoms, although only to a minor extent, are selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs). The intrusion symptom cluster, including nightmares, is reduced by prazosin, but it has little effect on other core symptom clusters. Severe mood disorders and psychotic comorbidities with PTSD may be stabilized with quetiapine and lamotrigine. In summary, it is MDMA and ketamine, under suitable clinical supervision, that show the greatest promise among the pharmacotherapies.