Regions and cities are increasingly interdependent; economically, socially and environmentally. They are, for example, becoming more reliant on interregional flows of trade, labour and resources. Patterns of interactions between regions are experiencing rapid changes as a result of dramatic shifts in production and consumption patterns, advances in communication technologies and the development of transport infrastructure. These changes pose many challenges for the analysis and management of regions. They are also leading to new patterns of activities and relationships and new forms of clustering and networking between regions. At the same time, regions are becoming increasingly fragmented in many ways; economically, socially, environmentally and also politically. Classic forms of government based on clear cut arrangements between administrative levels, policy sectors and the public and private domain are no longer sufficient. The governance of regions faces multi-level, multi-actor and multi-sectoral challenges. New spatial interactions at new scales demand new approaches for consultation and coordination. More flexible (‘softer’) forms of governance are beginning to emerge which seek to work around traditional governmental arrangements. The result is a complex pattern of overlapping governance and fuzzy boundaries, not just in a territorial sense but also in terms of the role of both public and private actors. These new arrangements pose many as yet unresolved dilemmas concerning the transparency, accountability and legitimacy of decision-making. The 2012 RSA conference in Delft provides a timely opportunity for participants to come together and reflect on the various strengths, weaknesses, challenges and opportunities of networked cities and regions within these different contexts of fragmentation.