This paper reviews the available data and models on energy and material flows through the world's 25 largest cities. Throughput is categorized as stored, transformed, or passive for the major flow modes. The aggregate, fuel, food, water, and air cycles are all examined. Emphasis is placed on atmospheric pathways because the data are abundant. Relevant models of urban energy and material flows, demography, and atmospheric chemistry are discussed. Earth system-level loops from cities to neighboring ecosystems are identified. Megacities are somewhat independent of their immediate environment for food, fuel, and aggregate inputs, but all are constrained by their regional environment for supplying water and absorbing wastes. We elaborate on analogies with biological metabolism and ecosystem succession as useful conceptual frameworks for addressing urban ecological problems. We conclude that whereas data are numerous for some individual cities, cross-cutting compilations are lacking in biogeochemical analysis and modeling. Synthesis of the existing information will be a crucial first step. Cross-cutting field research and integrated, multidisciplinary simulations will be necessary.