This chapter highlights the breadth of the range and shallowness of the depth with which novel therapeutics for PTSD have been evaluated. None of the new treatments reviewed in this chapter have sufficient data supporting their efficacy to be strongly recommended for the treatment of PTSD. Nonetheless, the interventional approaches reviewed here are guided by our current understanding of the neurobiology of stress in animals and PTSD in humans. The range of therapeutic targets considered in this chapter reflects our growing appreciation of the complex neurobiology of PTSD. Thus, it should not be surprising that drugs targeting glutamatergic, GABAergic, opiates, glucocorticoids, cannabinoids, and voltage-gated calcium channels are in various stages of evaluation.