Post-traumatic stress disorder (PTSD) is frequently chronic and associated with significant morbidity, poor quality of life, and high personal, social, and economic costs. It additionally represents a risk factor for developing other mood and anxiety disorders, as well as substance-use disorders. The clinical utility of the monoamine oxidase inhibitors (MAOIs) is limited by the potential for serious drug-related adverse events, such as hypertensive crises, and stringent dietary restrictions. These shortcomings have been largely overcome in the case of the reversible inhibitors of monoamine oxidase A (RIMAs), with their more selective inhibition of monoamine oxidase A reuptake. The majority of the evidence of efficacy was for the selective serotonin reuptake inhibitor (SSRIs), with paroxetine reducing symptom severity to a greater extent than sertraline. There has recently been interest shown in the treatment of PTSD with medications that employ extra-serotonergic mechanisms of action, including the anticonvulsants, atypical antipsychotics, and venlafaxine.