Post-traumatic stress disorder (PTSD) is a common, debilitating condition with symptoms that cause substantial stress or functional impairment. Currently, paroxetine and sertraline are the only medications approved in the USA for the treatment of PTSD, but their efficacy is limited and there is an unmet need for new pharmacological options. Several pathophysiological pathways and processes of PTSD have been highlighted as targets for potential drug development, including brain hyper- and hypoactivity, the hypothalamic-pituitary-adrenal axis and the endocannabinoid system. The use of psychedelics in combination with psychotherapy are also being investigated for the treatment of PTSD.