The nation's 12 largest urban regions, located throughout the continental United States, make up the essential core of the American economy. With few exceptions, they are America's major centers of innovation and technological advancement. Yet they are also at the front line of demographic change: they house the bulk of the country's new immigrants, they deal with evolving family and household relationships, and they cope with major growth in the nation's elderly population. Collectively home to 90 million inhabitants--a population greater than that of Mexico or Germany--the 12 largest regions and their 14 central cities represent a significant force in the global economy. In this paper a brief overview of the economic and social relevance of the nation's largest cities and their urban regions is presented. Although some cities, independent of their surrounding suburban areas, would not rank among the largest in population terms, their importance is established through their status as the central cities of the largest urban agglomerations. Because the two--city and region--are so inextricably bound, the focus in this paper is on socioeconomic trends and conditions in both areas.