This Series shows how racism, xenophobia, discrimination, and the structures that support them are detrimental to health. In this first Series paper, we describe the conceptual model used throughout the Series and the underlying principles and definitions. We explore concepts of epistemic injustice, biological experimentation, and misconceptions about race using a historical lens. We focus on the core structural factors of separation and hierarchical power that permeate society and result in the negative health consequences we see. We are at a crucial moment in history, as populist leaders pushing the politics of hate have become more powerful in several countries. These leaders exploit racism, xenophobia, and other forms of discrimination to divide and control populations, with immediate and long-term consequences for both individual and population health. The COVID-19 pandemic and transnational racial justice movements have brought renewed attention to persisting structural racial injustice.