The recent worldwide surge of warfare and hostilities exposes increasingly large numbers of individuals to traumatic events, placing them at risk of developing posttraumatic stress disorder (PTSD) and challenging both clinicians and service delivery systems. This overview summarizes and updates the core knowledge of the genetic, molecular, and neural circuit features of the neurobiology of PTSD and advances in evidence-based psychotherapy, pharmacotherapy, neuromodulation, and digital treatments. While the complexity of the neurobiology and the biological and clinical heterogeneity of PTSD have challenged clinicians and researchers, there is an emerging consensus concerning the underlying mechanisms and approaches to diagnosis, treatment, and prevention of PTSD. This update addresses PTSD diagnosis, prevalence, course, risk factors, neurobiological mechanisms, current standard of care, and innovations in next-generation treatment and prevention strategies. It provides a comprehensive summary and concludes with areas of research for integrating advances in the neurobiology of the disorder with novel treatment and prevention targets.