The Genomic Data Infrastructure (GDI) project brings together national agencies, research organizations, and technology providers in 22 countries to provide a cross-border federated network of national genome collections, associated with other relevant data, for advancing data-driven biomedical research and personalized medicine solutions to benefit citizens of Europe. The project is designed to support the European 1+ Million Genomes (1+MG) Initiative. Specifically, GDI will drive the development, deployment, and operation of sustainable data-access infrastructures within each participating country including the legal frameworks, operational procedures and ethics principles required to foster and maintain citizens’ trust in cross-border access to highly sensitive personal data. It will unlock a data network of over 1 million genome sequences for research and clinical reference creating unprecedented opportunities for routine transnational, multi-stakeholder actions in personalized medicine for common, rare, and infectious diseases. Authorized data users, such as clinicians, researchers, and innovators, will be able to advance our understanding of genomics for more precise and faster clinical decision-making, diagnostics, treatments, and predictive medicine, and for improved public health measures that will benefit citizens, healthcare systems and the overall economy. Thus, GDI is one critical component of Europe’s ambition to lead the integration of genomics into healthcare and the GDI project is designed to interact with the other actors working towards this ambition via incremental milestones that drive alignment along a dynamic roadmap.