Social entrepreneurship is key to the success of health promotion and Healthy City development. An overview of entrepreneurial skills is provided, and a policy change model in which social entrepreneurs play a key role is described. The model has been tested in a selection of 10 European, officially WHO-designated, Healthy Cities. Recognition by the entrepreneur of the components of the model, and subsequent strategic action, indeed influenced urban policy agendas. However, the two cities that were most effective in doing so also had institutionalized their entrepreneurial capacities. This seems therefore the next challenge in health promotion.