Early recognition and treatment of posttraumatic stress disorder (PTSD) in youth are critical. This article provides a comprehensive overview of the up-to-date evidence for pharmacological options for children with PTSD. Eight electronic databases were searched and a manual search of the full text of included articles was performed. Two independent reviewers performed screening of the articles using the predetermined eligibility criteria. The data were extracted by two independent reviewers. The search generated 32 articles with a total patient population of 833. The pharmacological options were antidepressants, antipsychotics, mood stabilizers, alpha-adrenergic agents, beta-blockers, serotonin and histamine antagonists, and opioid agonists. The mood stabilizers and second-generation antipsychotics should be reserved for patients with significant safety concerns or aggressive behaviors because of their side-effect profile. Alpha-adrenergic agonists can be used in patients who are re-experiencing symptoms of PTSD and without safety concerns. [ Psychiatr Ann . 2020;50(5):209–228.]