Cities are the predominant mode of living, and the growth in cities is related to the expansion of areas that have concentrated disadvantage. The foreseeable trend is for rising inequities across a wide range of social and health dimensions. Although qualitatively different, this trend exists in both the developed and developing worlds. Improving the health of people in slums will require new analytic frameworks. The social-determinants approach emphasizes the role of factors that operate at multiple levels, including global, national, municipal, and neighborhood levels, in shaping health. This approach suggests that improving living conditions in such arenas as housing, employment, education, equality, quality of living environment, social support, and health services is central to improving the health of urban populations. While social determinant and multilevel perspectives are not uniquely urban, they are transformed when viewed through the characteristics of cities such as size, density, diversity, and complexity. Ameliorating the immediate living conditions in the cities in which people live offers the greatest promise for reducing morbidity, mortality, and disparities in health and for improving quality of life and well being.