In 2008, the world’s urban population exceeded its rural population for the first time. The United Nations estimates that about 15% of the world’s population now lives in “megacities” of 10 million or more people, or in near-megacities of 5-10 million. Three-quarters of the megacities are in low- and middle-income nations, where rural-to-urban migration will drive rapid urbanization through 2050. Services and infrastructure rarely keep pace with population growth. Even in well-resourced cities, municipal leaders struggle with urban sprawl, unmet housing and transportation needs, environmental degradation, and disaster vulnerabilities. In the absence of adequate resources and regulation, informal settlements and markets evolve fluidly, creating shelter and livelihoods but also exposing inhabitants to environmental risks that exacerbate health inequities. These problems might once have been considered local challenges. Now, these “international cities” are often cross-roads for the movement of people, animals, and goods (and the health risks that they carry), as well as drivers of national or regional economic development. New strategies are needed to govern the flow of health risks within and among these densely populated urban centers. The breathtaking scope of the challenges that urbanization poses for development and security can only be understood by looking at long wave events that cross sectors, disciplines, and borders. Tools such as the Framework Convention on Tobacco Control and the International Health Regulations (2005) can affect the flow of health risks between regions, but cannot substitute for strong planning, policy, and management functions at the municipal level – exactly where governance capacities tend to be weakest.