There are known disparities in the burden of illness and access/quality of care for African, Latino/a, Asian, and Native American (ALANA) patients diagnosed with depressive disorders, which may occur because of health inequities. Racial stress and trauma (RST), or the significant fear and distress that can be imparted from exposure to racism, is one such inequity linked to the development of depression. The current review summarizes past research examining the association between racism, RST, and depression, as well as avenues in which RST becomes biologically embedded in ALANA individuals. We describe multimodal research that supports vigilance as a potential mediator of the association between RST and depression and consider the nuanced role that vigilance plays during experiences with racism. Finally, we describe methodological advances in the assessment of vigilance evoked by RST and the clinical implications that may be generated by future improvements. In each of these areas, we present examples of how ongoing and future research can be leveraged to provide support for psychosocial programs that facilitate autonomous community healing and resilience, increase calls for public policy changes, and support clinical interventions that lessen the burden of racism on ALANA communities.