Traumatic events are ubiquitous exposures that interact with life course events to increase risk of acute psychopathology and alter mental health trajectories. While the majority of persons exposed to trauma experience mild to moderate psychological distress followed by a return to pre-trauma health, many persons exposed to trauma experience substantial distress that lasts for several years. Therefore, in an effort to understand why exposure to trauma can provoke such a range of reactions, we apply a life course approach that considers the complex accumulation and interaction of life experiences that range from social to biological factors, which occur over the life span-from gestation to death and across generations. We present this evidence in three categories: genetics and biology, individual exposures, and community experiences, followed by discussing challenges in existing research and directions for future study.