The 2016 decision by the United Kingdom to withdraw from the European Union was a seminal one for both parties. In this special issue, we consider the extent to which the inter-penetration of the national and the European arenas produced significant opportunities for recasting political action. The nesting of these two levels matters firstly in allowing for the politicisation and mobilisation of domestic actors around European issues and secondly in explaining why seemingly sub-optimal or counter-productive actions are taken. The tensions this generated reached a critical juncture with the referendum, a rupture that highlights the extent to which a nominally second-order vote can have fundamental impacts on the first order’s structure and preferences. Bringing together scholars from a wide range of approaches and covering various aspects of the Brexit process, this special issue offers a significant contribution to improving our understanding of an event that will shape British and European politics for a generation.