Regional and/or national severe asthma registries provide valuable country-specific information. However, they are often limited in scope within the broader definitions of severe asthma, have insufficient statistical power to answer many research questions, lack intraoperability to share lessons learned, and have fundamental differences in data collected, making cross comparisons difficult. What is missing is a worldwide registry which brings all severe asthma data together in a cohesive way, under a single umbrella, based on standardized data collection protocols, permitting data to be shared seamlessly. The International Severe Asthma Registry (ISAR; http://isaregistries.org/) is the first global adult severe asthma registry. It is a joint initiative where national registries (both newly created and preexisting) retain ownership of their own data but open their borders and share data with ISAR for ethically approved research purposes. Its strength comes from collection of patient-level, anonymous, longitudinal, real-life, standardized, high-quality data (using a core set of variables) from countries across the world, combined with organizational structure, database experience, inclusivity/openness, and clinical, academic, and database expertise. This gives ISAR sufficient statistical power to answer important research questions, sufficient data standardization to compare across countries and regions, and the structure and expertise necessary to ensure its continuance and the scientific integrity and clinical applicability of its research. ISAR offers a unique opportunity to implement existing knowledge, generate new knowledge, and identify the unknown, therefore promoting new research. The aim of this commentary is to fully describe how ISAR may improve our understanding of severe asthma.