Post-traumatic stress disorder (PTSD) is increasingly recognized as a serious and potentially debilitating condition in combat veterans returning from Iraq and Afghanistan. Exposure to a potentially life-threatening event such as military combat may be followed by PTSD. Despite recent advances in pharmacotherapy for PTSD, monotherapy with the currently available medications is only partially effective, as demonstrated in large clinical trials of combat veterans with PTSD. This underscores the need to investigate novel combination strategies to enhance treatment response in PTSD. The α-1 adrenergic receptor (AR) antagonist, prazosin, appears promising in recent studies for its capacity to reduce trauma-related nightmares (a group B night-time intrusion symptom) and insomnia (a group D night-time arousal symptom), while recent evidence supports using the β-AR antagonist, propranolol, to dampen the emotional content of traumatic memories (daytime intrusion symptoms including flashbacks, intrusive recollections of traumatic event, and heightened physiological reactivity/ responsivity to trauma reminders). In this review, we present data supporting the potential utility of combined drug regimen (prazosin and propranolol) acting through different noradrenergic mechanisms, with the potential to target more than one set of PTSD symptoms to optimize PTSD treatment.