The majority of the world's population will live in cities in the next few years, and the pace of urbanization worldwide will continue to accelerate over the coming decades. Such a dramatic demographic shift can be expected to have an impact on population health. Although there has been historic interest in how city living is associated with health, this interest has waxed and waned and a cogent framework has yet to evolve that encompasses key issues in urban health. In this article, the authors discuss three alternate approaches to the study of urban health today; these include considering urban health from the perspective of a presumed urban health penalty, from an urban sprawl perspective, and more comprehensively, considering how urban living conditions may be associated with health. The authors also propose three key questions that may help guide the study and practice of urban health in coming decades. These include considering what specific features of cities are causally related to health, the extent to which these features are unique to a particular city or are different between cities, and ultimately, to what extent these features of cities are modifiable in order to allow interventions that can improve the health of urban populations.