In European politics, the idea of a ‘Europe of the Regions’ came to the fore in the 1980s and early 1990s, in response to innovative policy and institutional developments in European integration. Different subnational actors saw in these developments the potential for creating an alternative supranational framework for meeting their territorial and other policy goals. Scholars of the European Union were also inspired to develop new theories and concepts for explaining decision making within a multi-level European polity. In recent years, however, as the limitations for regional mobilization within the EU have become more apparent, the notion of a ‘Europe of the Regions’ has fallen out of favour. One unfortunate consequence of this has been that the regional dimension of European politics has become increasingly neglected. This Introduction makes the case for the need to revisit the regional dimension to European politics. After summarizing the rise and fall of the ‘Europe of the Regions’ idea, the numerous ways in which the EU remains highly important for regions, and in which regional politics plays a significant role in shaping the nature and direction of European integration, are outlined. The Introduction concludes by summarizing how the contributions to this Special Issue take up the challenge of re-examining this regional dimension within an ever-changing and ever-expanding Europe.