Posttraumatic stress disorder (PTSD) is a common, frequently chronic, and disabling condition which, along with acute stress disorder (ASD), is categorized as a trauma- and stressor-related disorder by the DSM-5. These disorders are unique in requiring exposure to a severe stressor, which implies that potential sufferers could be identified and helped before developing a disorder. Research on prevention strategies for stress-related disorders has taken a number of avenues, including intervention before and after trauma and the use of both psychosocial and somatic approaches. Despite advances in neurobiological understanding of response to trauma, clinical evidence for preventive interventions remains sparse. This review provides an overview of prevention approaches and summarizes the existing literature on prevention of ASD and PTSD, including clinical and preclinical studies. Given the potential benefits to trauma survivors and society, the development of effective preventive interventions should be given greater priority. Resources should be directed to adequately test promising interventions in clinical trials, and research should be conducted according to translational research principles in which preclinical research informs the design of clinical studies.