Objective A central adrenergic hyperactivation is described in the neurobiology of posttraumatic stress disorder (PTSD) with probable variable symptomatic impact. Few studies have evaluated using the alpha-1 adrenergic antagonist prazosin for such symptoms; however, given the likely pathophysiology involved, this drug may play an important role in the pharmacological approach to PTSD. Methods This study assessed articles already published on the use of prazosin through a systematic review along a timeline in view of the symptomatic target of difficult access by standardized treatments. The impact of using this medication for the general symptoms of PTSD is also discussed. Several databases were searched for articles in the literature on the use of prazosin to treat PTSD. Results A total of 168 articles were found containing search terms in the title or abstract. Overall, 85 articles met the criteria described, and 48 studies were explored to conduct the present systematic review. Most articles showed some improvement after prazosin administration, especially in relation to sleep symptoms (nightmares and night waking). Only one article demonstrated no improvement after the use of this drug. More randomized studies are needed. Conclusion Several clinical studies demonstrated the relevant role of prazosin for treating PTSD symptoms. Prazosin is an affordable and cost-effective pharmacological option compared to other drugs used to treat PTSD.