A number of changes in the environment of the WHO’s Regional Office for Europe (WHO EURO), and the entering into office of a new Regional Director on 1 February 2010, provide a good opportunity to rethink strategic governance questions of the organisation. This paper aims to increase understanding of how these changes impact on WHO EURO, what questions they pose, and what options exist to address them. It addresses its formal-legal and moral authority, as well as its legitimacy base, and considers how the organisation could position itself and work together with the many other actors that today are working on health issues in the European region, with a view of moving the health agenda forward. Changes discussed are the new multi-polar world order, heterogeneity in the region, increased interdependence and competition, health as a critical policy domain, an increase of health actors, the growth of health industry, and effective multilateralism and UN reform. In the past, such changes have caused organisational change. WHO EURO has shifted from a classical technical health organisation established in the aftermath of the second world war, first to a more innovative organisation covering the health issues of a prosperous region, and second to a decentralised organisation focused on helping countries to adjust health systems after the fall of the Berlin wall. At this period in time, the EU obtained a (modest) health mandate and expanded its membership. We identify six strategic responses that need to be addressed today: i) strengthening governance ii) intensifying the global - regional interface; iii) (re)positioning in the region iv) stakeholder management; v) new health priorities; and vi) financing. In recent years, the EU role in health has expanded drastically and EU Member States nowadays form a majority within the Regional Committee of WHO EURO. Other countries align their policies to those of the EU, because they want to obtain membership, EU finances or other benefits. In combination with a reform of the system of EU external relations following from the entry into force of the Lisbon Treaty, this asks for a reconsideration of the EU-WHO (EURO) relationship. A strategic partnership could be established. Within WHO EURO, the majority threshold could be adjusted and more consultation with non-EU members should be warranted, for instance by means of a strengthened SCRC. We argue that WHO EURO should be reorganised into a networked organisation. Internally, the Copenhagen Office needs to be strengthened. The work of GDOs and country offices could be decreased and become more aligned to that of the Copenhagen Office. A critical aspect is to bind external actors through flexible expertise-networks to WHO EURO. The field of actors is rather crowded and fragmented today and in the paper, and in Annex 3, we have made a first attempt to consider which actors set health standards, which analyse data and provide health advise and which are financing health. WHO EURO finally also has a role towards global governance issues. Its relationship with WHO Headquarters in Geneva, as well as to other organisations of the UN family, implies certain roles and responsibilities, but also creates opportunities to advocate EURO preferences. The relationship between health and other policy areas, such as security, trade, social-economic and environmental policies is two-dimensional as well. Good health provides benefits, but changes in the other sectors, such as stability and economic growth and equity, are necessary in order to achieve a good level of health for all people. Coherence is thus essential. The relationship between health and foreign policy is most relevant in this respect for the work of WHO EURO, which could also contribute positively to inter-regional relations and make the wealth of expertise available within the region available to others.