As part of the European Commission’s Open Strategic Autonomy agenda, the European Union has reformed its unilateral trade and investment policy toolbox. Existing instruments have been updated (e.g., Trade Defence Instruments, the Enforcement Regulation) and new instruments have been adopted (e.g., the Foreign Subsidies Regulation, the Foreign Direct Investment Screening Regulation, the Anti-Coercion Instrument). These developments are significant: taken together, they herald a unilateral turn in the EU’s trade and investment policy. This special issue explores aspects of this unilateral turn. It combines a bird’s-eye perspective with studies of specific instruments; it brings together political science and legal methodologies; and it looks at the unilateral turn from the inside-out and from the outside-in. The special issue scratches the surface of what we consider to be a seismic change in the EU’s trade and investment policy. We hope it will trigger further debate and scholarly analysis of this important topic. In this introduction, we set the scene and introduce the six articles that are part of this special issue.