Post-traumatic stress disorder occurs in patients who have undergone a traumatic experience and manifests itself through a cluster of symptoms, including re-experiencing, avoidance and hyperarousal. Post-traumatic stress disorder is commonly found among veterans of war and victims of sexual trauma, natural disasters and accidents. Nefazodone is a medication that has an FDA-approved indication for treating depression. Nefazodone has also been reported to be efficacious in treating post-traumatic stress disorder. Despite recent reports of hepatotoxicity, when used appropriately, nefazodone is generally as well-tolerated as the medications currently FDA-indicated for post-traumatic stress disorder, the selective serotonin reuptake inhibitors. Through its mechanism inhibiting neuronal uptake of serotonin and norepinephrine and as a potent postsynaptic serotonergic antagonist, nefazodone has proven to be effective in treating post-traumatic stress disorder in several open-label trials. The results of such trials warrant its study in larger, double-blind, placebo-controlled clinical trials.