Established domestic regulatory frameworks are reaching their limits to cope with today’s increasing cross-boundary policy challenges. Only united action can effectively navigate the rapid growth of economic integration and interdependencies, particularly driven by innovative technologies. Yet, contemporary regulatory frameworks tend to build on national jurisdictional boundaries constraining common solutions to meet the growing transboundary nature of policy challenges. In the aftermaths of global crises, such as the 2008 financial crisis or the COVID-19 pandemic, which exposed the vulnerabilities of global health, economic and governance systems, it is time for a true paradigm shift towards more systematic consideration of the international environment in domestic regulatory frameworks. The OECD Best Practice Principles on International Regulatory Co-operation provide practical guidance supporting policy makers and civil servants in adapting regulatory frameworks to the interconnected reality. They outline key elements in defining a dedicated whole-of-government strategy and governance structure, embedding international considerations throughout the domestic regulatory design, development and delivery, and leveraging bilateral, regional and multilateral international co-operation on regulatory matters to support national policy objectives. Compiling various ways of international regulatory co-operation and experiences from countries, the OECD Best Practice Principles on International Regulatory Co-operation provide impetus for policy makers and civil servants in a variety of legal and administrative environments on how to promote quality and resilience of regulatory frameworks in times of an increasingly interconnected world.