This article examines how segregation contributes to the perpetuation of disadvantage over time and across generations. It first traces the historical origins of segregation and reviews early substantive and theoretical work done on the subject at the University of Chicago. It then considers the most commonly used measure of segregation as well as the social mechanisms by which residential segregation is produced, with particular emphasis on the paradigmatic case of African Americans in the twentieth century. It also discusses newer mechanisms that have been advanced to promote racial-ethnic segregation in the twenty-first century and how it fosters socioeconomic inequality through the spatial concentration of poverty. Finally, it describes current levels and trends with respect to both racial and class segregation in cities around the world.