Post-traumatic stress disorder (PTSD) is a prevalent psychiatric disorder that may result in significant social and occupational debilitation unless symptoms are recognized and treated appropriately. Considerable research effort has been devoted over the last 20 years to developing effective pharmacological treatments for this illness. At this time, the bulk of the agents investigated include antidepressants, anticonvulsants, atypical antipsychotics, benzodiazepines, and antiadrenergic agents. Herein, we review the existing evidence base for these different classes of psychotropics in PTSD. Emphasis is placed on discussion of evidence stemming from randomized placebo-controlled clinical trials wherever possible. A brief description of novel agents that have shown initial promise for PTSD treatment is also provided.