European integration is a fundamentally open-ended and contested process. Within the ‘mosaic of European integration theories’, critical political economy perspectives highlight the imbalances and structural power asymmetries of the European project, and how they have become manifest in the multiple crises in Europe. How to account for both the origins and consequences of this crisis has become a key question for scholars and students of European integration. We argue that critical political economy (CPE) has an important and unique contribution to make here. Unlike other approaches, CPE seeks to uncover the deep connections between the (internal) dynamics of the European integration process and the dynamics of global capitalism, arguing that European integration, or disintegration for that matter, takes place in a global, structural context that shapes and conditions both form and content of the integration process. In this paper, we provide an overview of the key concepts, methodology and arguments of a critical political economy perspective on European integration. Following a discussion of the core conceptual framework, the paper then proceeds with an integrated analysis of EMU as a political project, with a particular focus on continuity and changes within the political economy of neoliberalism. The Euro crisis here serves as a contemporary reference point to illustrate the strengths and contributions of critical political economy perspectives to the overall mosaic of European integration theories.