The continent of Africa is the source of all anatomically modern humans that dispersed across the planet during the past 100,000 years. As such, African populations are characterized by high genetic diversity and low levels of linkage disequilibrium (LD) among loci, as compared to populations from other continents. African populations also possess a number of genetic adaptations that have evolved in response to the diverse climates, diets, geographic environments, and infectious agents that characterize the African continent. Recently, Tishkoff et al. (2009) performed a genomewide analysis of substructure based on DNA from 2432 Africans from 121 geographically diverse populations. The authors analyzed patterns of variation at1327 nuclear microsatellite and insertion/deletion markers and identified 14 ancestral population clusters that correlate well with self described ethnicity and shared cultural or linguistic properties. The results suggest that African populations may have maintained a large and subdivided population structure throughout much of their evolutionary history. In this chapter, we synthesize recent work documenting evidence of African population structure and discuss the implications for inferences about evolutionary history in both African populations and anatomically modern humans as a whole.Africa is a continent of considerable genetic, linguistic, cultural, and phenotypic diversity. It contains more than 2000 distinct ethnolinguistic groups, speaking languages that constitute nearly a third of the world's languages (http://www.ethnologue.com/). The populations within Africa practice a wide range of subsistence patterns, including various modes of agriculture, pastoralism, and hunting and gathering. Africans also live in climates that range from the world's largest desert (the Sahara) and second largest tropical rainforest (the Congo Basin) to savanna, swamps, and mountain highlands. This dramatic range in culture, geography, and diet has given rise to a complex history across the African continent, characterized by high levels of both genetic and phenotypic variation.Africa is also the source of all modern humans, making its populations the oldest and most genetically diverse among the world's human populations. According to the Recent African Origin (RAO) model, anatomically modern humans originated in Africa and then migrated to all other regions of the globe within the past ∼100,000 years (Tishkoff and Verrelli 2003). The transition to modern humans within Africa was not sudden. Rather, the paleobiological record indicates an irregular mosaic of modern, archaic, and regional traits occurring over a sub stantial period of time and across a broad geographic range (McBrearty and Brooks 2000). The earliest known suite of morphological traits associated with modern humans appears in fossil remains from Ethiopia that are dated to ∼150-190 thousand years ago (kya) (White et al. 2003; Correspondence to: S.A. Tishkoff, tishkoff@mail.med.upenn.edu. Patterns of genetic variation in modern ...