Racial residential segregation is a fundamental cause of racial disparities in health. The physical separation of the races by enforced residence in certain areas is an institutional mechanism of racism that was designed to protect whites from social interaction with blacks. Despite the absence of supportive legal statutes, the degree of residential segregation remains extremely high for most African Americans in the United States. The authors review evidence that suggests that segregation is a primary cause of racial differences in socioeconomic status (SES) by determining access to education and employment opportunities. SES in turn remains a fundamental cause of racial differences in health. Segregation also creates conditions inimical to health in the social and physical environment. The authors conclude that effective efforts to eliminate racial disparities in health must seriously confront segregation and its pervasive consequences.