The European and American economies are closely interlinked as mutually important investment and trading partners. The growing intensity of economic interdependence has spurred the transatlantic coordination of rules and standards that can lead to the formation of non-tariff barriers to transatlantic commerce. But despite impressive government-to-government efforts to eliminate market barriers, the E.U. and the U.S. have frequently clashed over each other’s regulatory policies. The aim of this book is to explore the domestic sources of cooperation or conflict in transatlantic regulation. The book analyses the role of domestic factors through three theoretical lenses that are well-established in the study of multilevel systems: the principal-agent approach, the two-level game metaphor, and through a wider concept of institutionalism which emphasises the links between societal interests and regulatory ideas with institutional frameworks. The book states that domestic factors embody more obstacles than opportunities for horizontal coordination. It is argued that transatlantic relations will likely undergo a ‘double movement’ of being simultaneously shifted upwards to become part of the global governance architecture, and downwards towards broader involvement of legislators in regulatory matters. Hence, transatlantic regulation might in the near future be shaped more by political leaders, rent-seeking interest groups and legislators than by networks of technocrats.This book was published as a special issue of the Review of International Political Economy.