This special issue of Meridians offers a unique opportunity to reflect on the complexity of black women’s racialized and gendered health landscapes in light of relevant social and political contexts and conventions about: a) what constitutes research excellence, and b) how and by whom credible research is created. Throughout my forty-plus years of academic life, I have been repeatedly and sometimes painfully reminded of the importance of ongoing critical reflection on what it will take for black health researchers to generate evidence that will have major impacts on the health of black communities and individuals. US black women’s reproductive outcomes, health risk factors, disease occurrence, and survival after disease onset reflect multiple disadvantages when compared with US white women and, in some cases, with black men. These disadvantages can be understood as legacies of racially-biased and discriminatory US social and economic policies, practices, and attitudes dating back to black enslavement. Underlying causes of pervasive and persistent health disparities affecting the US black population are generally not acknowledged or are underestimated, including within academic circles. Black women’s health researchers, therefore face ongoing challenges of studying disparities in ways that take these underlying causes into account, while recognizing that such research may be met with resistance in various forms. Furthermore, research that addresses the diverse, dynamic, and intersectional causes of black women’s health problems will require multisectoral, multilevel, and interdisciplinary collaborations that extend beyond the boundaries and discipline-specific paradigms of the academic silos that typically control academic reward systems. I envision a future black women’s health research agenda that emanates from such a systems paradigm. The agenda would frame black women’s health and well-being as emerging from complex interactions among several causal factors acting at multiple levels and shifting over time. I believe that black women academics and those who link arms with us to address black women’s health issues have the capacity to succeed in generating major and long-lasting improvements in black women’s health, but only if we radically shift our approach to be systems-oriented. Current approaches may produce isolated successes, but these can easily be attenuated by the larger, unfavorable systems in which they occur. This vision is timely considering current US and global attention to social determinants of health and to achieving overall health equity. There are great opportunities, individually and (especially) collectively, to build on learnings from past decades and leverage today’s research tools to impact upon current and emerging black women’s health issues.