Segregation is one form of stratification in a society, and is a complex phenomenon resulted from multiple societal forces at work. In this chapter, we highlight the pervasiveness of segregation across different socio-geographical spaces and between population groups classified according to socio-demographic characteristics. We review some issues related to the measurement of segregation, particularly the inability of traditional measures in capturing the spatial nature of segregation. Using data from two cities in the United States, we demonstrate how the local spatial isolation index (SIi) can be used to assess the interplay between racial-ethnic and socio-economic groups at the neighbourhood (or local) level. Analyzing relationships between these population groups can provide valuable information toward the understanding of the complexity of segregation in today’s increasingly stratified societies.