Black Americans experience diverse racism-related stressors throughout the lifespan. Disproportionately high trauma exposure, economic disadvantage, explicit racism and inequitable treatment are stressors faced by many Black Americans. These experiences have a cumulative negative impact on psychological and physical health. However, little is understood about how experiences of racism, such as discrimination, can mediate health outcomes via their effects on neurobiology. I will present clinical, behavioral, physiological and neurobiological data from Black American participants in the Grady Trauma Project, a longstanding study of trauma conducted in inner-city Atlanta. These data will be discussed in the context of both risk and resilience/adaptation perspectives. Finally, recommendations for future clinical neuroscience research and targets for intervention in marginalized populations will be discussed.