This article synthesizes diverse official reports, statistics, and scientific papers that present demographic, economic, environmental, and social trends impacting on the health and quality of life of citizens living in European cities. A literature review led to the identification of some key challenges including an aging society, migration flows, inequalities in health, global change, and risk behaviors that should be addressed in order to promote urban health. Other challenges, such as food production and consumption, are also relevant, but not included. Cities that have participated in one or more of the phases of the WHO European Healthy Cities Network have implemented a number of policies, programs, and measures to deal with the challenges discussed in this article. Some contributions are presented to illustrate how health and quality of life in urban areas can be promoted by local authorities.