We present an evidence-based review of post-trauma interventions used to prevent posttraumatic stress disorder (PTSD). Literature search of PubMed from 1988 to March 2016 using keywords “Early Intervention AND Prevention of PTSD” yielded 142 articles, of which 52 intervention studies and 6 meta-analyses were included in our review. Trauma-focused cognitive behavioral therapy and modified prolonged exposure delivered within weeks of a potentially traumatic event for people showing signs of distress have the most evidence in the treatment of acute stress and early PTSD symptoms, and the prevention of PTSD. Even though several pharmacological agents have been tried, only hydrocortisone prior to high-risk surgery, severe traumatic injury, or during acute sepsis has adequate evidence for effectiveness in the reduction of acute stress symptoms and prevention of PTSD. There is an urgent need to determine the best targets for interventions after trauma to accelerate recovery and prevent PTSD.