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As a response to the Russian invasion of Ukraine, the United States and the European Union have put in place far-reaching and highly coordinated sanctions against Russia. While their sanctions are similar in content, the United States and the European Union differ in their sanctions’ history as well as in their respective sanctions frameworks, which govern how sanctions are adopted, implemented, and challenged. These frameworks constitute the backbone of the sanctions imposed and shape their effectiveness and impact. They therefore are critical for the United States’ and the European Union’s capacity to conduct geopolitics. This article explores the sanctions frameworks of the United States and the European Union from a comparative perspective and investigates their similarities and differences. It argues that the post 2022 sanctions against Russia are in many ways a turning point for the European Union’s sanction practice, uncovering considerable insufficiencies, but also sparking critical reflection and much needed innovation. It furthermore underscores that a good look at the long-serving United States’ sanctions framework will pay off for the European Union, when creating the foundation for future sanctions regimes.