The modern human appeared in Africa around 200,000 years ago with subsequent later migrations to populate Europe, Asia, and North America. 1 As humans adapted to various diets, diseases, climates, and so on, inherited traits emerged that gave rise to distinct population groups with physical and physiological differences, including the response to xenobiotic challenges (Figure 1). This Perspective highlights the interpopulation differences in response to drugs focusing on Africa and implications for global pharmacometric studies.