The world is undergoing a massive urban transition, which is now both the greatest driver of global environmental change and the most significant influence on human health. Cities offer real opportunities for improving health, but managed poorly, they can also create or reinforce significant health deficits while putting severe stresses on the natural systems which support human civilization. Management of urban problems is rarely straightforward, as complexity across scales and sectors, in causal structures, actors and incentives, can lead to ineffective policies and unintended consequences. Systems thinking offers a promising way forward in its ability to deal with non-linear relationships and simultaneous actions and outcomes. Encompassing, on the one hand, analytic frameworks and methods that can provide important causal insights and a test bed for urban policy, and on the other, broad processes of inter- and trans-disciplinary engagement to better define problems and feasible solutions, systems approaches are critical to the current and future design and management of sustainable healthy cities.