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This article considers the impact of globalization on American cities and how these cities will function and compete in a global economy. It argues that almost all American cities grew from an original economic raison d’être, greatly shaped by the industrial era. The end of that era and the arrival of a new economy affect their utility, for better or worse. Secondly, most American cities are place-based, rooted in areas where they can take advantage of nearby raw materials and serve trade routes and surrounding communities. Global cities will, by necessity, need to sever these geographical ties and find new places in a global network less connected to their environs. American cities such as New York, Chicago, Los Angeles and to a lesser extent Boston, Houston and Atlanta, are moving in this direction. A second category of regional capitals will remain more local than global, like Indianapolis, Columbus, Portland and the like. A third category includes once-powerful industrial cities such as Detroit and Cleveland, which lack both global connections and prominent regional status. Their future will be problematic. The final section of the article describes what these cities must do to cope in the future. The emphasis here is on global cities that must find new ways to finance themselves as their old ties to state governments wither.