The CITYREGIO projects increase the capacities of participating city-regions and to spur their economic development. Intended outcomes are regional location information systems, feasibility studies for strategic investments, and the clustering of SMEs. Whereas important steps were taken in the first CITYREGIO project (2003 – 2006), involving partners from the city-regions of Leipzig (DE), Pilsen (CZ) and Linz (AT), the established profound knowledge base elaborated helps to move quickly towards the realisation of concerted economic (cluster) promotion activities, human resource management and location development initiatives within CITYREGIO 2 (2006-2008), where partners from the city-regions of Pilsen (CZ), Bologna (IT), Gdánsk (PL), Varna (BG), Leipzig (DE) and the South-Transdanubian Region (HU) participate.