The evidence is clear. On the whole, America's central cities are coming back. Employment is up, populations are growing, and many urban real estate markets are hotter than ever, with increasing numbers of young people, empty-nesters, and others choosing city life over the suburbs. Unfortunately, not all cities are fully participating in this renaissance. An examination of the performance of 302 U.S. cities on eight indicators of economic health and residential well-being reveals that 65 are lagging behind their peers. Most of these cities -- and their larger regions -- are older industrial communities that are still struggling to make a successful transition from an economy based on routine manufacturing to one based on more knowledge-oriented activities. Some others are simply dominated by the low-wage employment sectors that today characterize much of the American economy. But the outcomes are largely the same: While many of these cities have strong pockets of real estate appreciation and revitalization, on the whole they remain beset by slow (or no) employment and business growth, low incomes, high unemployment, diminishing tax bases, and concentrated poverty -- remnants of five decades of globalization and technological change, and the dramatic shift of the country's population away from the urban core. These cities weren't always in such a tenuous position. To the contrary, they were once the economic, political, and cultural hubs of their respective regions, and the engines of the nation's economic growth. They were vibrant communities where new ideas and industries were conceived and cultivated, where world-class universities educated generations of leaders, where great architecture and parks became public goods, and where glistening downtowns grew up within blocks of walkable, tree-lined neighborhoods, where the middle-class swelled and thrived. They were, in short, physical testaments to the innovation and spirit that shaped the nation and its citizens. And so they can be again. This report provides a framework for understanding how to restore prosperity in America's struggling cities, particularly those in the Northeast and Midwest. Targeted at state and local government, business, and civic leaders, this report describes the challenges facing these communities, the unprecedented opportunity that exists to leverage their many assets, and a policy agenda to advance their renewal.