This chapter sets out some of the key spatial politics that animate creative art practice in the UK. It looks particularly at the overwhelming focus on cities, either as historic art centres or more recent networks of competitive and self-branded ‘creative cities’, and at centre-periphery dynamics that work to rank and organise artists and artworks. It argues that understandings of ‘the region’ can be usefully employed to shift such dominant perspectives and to gain purchase on an overlooked, and far more complex and expansive, terrain. It further argues for an investigation of ‘the region’ as it is made to mean in everyday creative practice and not as represented in bodies of artistic work, via public policy or through grand acts of curation. To do this, the chapter draws upon empirical data collected from an artist-run initiative called Empty Shop in Durham, in the North East of England, UK – a city not particularly well-known for contemporary art. It explores the ways by which artists and other creative practitioners associated with Empty Shop navigated spatial divides and positions, the articulation of overlapping and ‘lived’ understandings of place and mobility and the significance of the meanings and values attached to ‘the region’ over time.