The EOSC Federation Handbook provides an overview of the organisational and operational structure and technical characteristics of the EOSC Federation. It aims to serve as a practical guideline for organisations that are interested in making their resources available within and across the EOSC Federation. Such organisations can achieve this objective by creating and operating an “EOSC Node”, and “enrolling” it as part of the EOSC Federation, and/or by “onboarding” their resources in one or more EOSC Nodes operated by other organisations. The intended users of the Handbook include primarily facility managers, policy makers and technical staff of research performing and funding organisations, research infrastructures, providers of scientific services and other resources, and e-infrastructures. The “end-users” of the resources accessible through the EOSC Federation, i.e. the researchers, are not directly targeted by the Handbook, but they may still find useful information about the scope and organisation of the EOSC Federation. It is important to build the EOSC Federation in the most transparent manner and with the understanding of the research community.