INFRAFRONTIER, the European Research Infrastructure for Modelling Human Diseases, stands as a pillar of collaborative effort and scientific excellence in the pursuit of understanding, prevention, and treatment of human diseases through cutting-edge models. The infrastructure is a non-profit entity comprising over 20 leading biomedical research institutes distributed across 15 countries: 13 of them in Europe (Austria, Czech Republic, Denmark, Finland, France, Germany, Greece, Italy, Netherlands, Portugal, Spain, Sweden, and United Kingdom), plus Israel and Canada. The INFRAFRONTIER GmbH, established in 2013 as a private limited company in Munich, Germany, is the coordination unit and central hub of the distributed INFRAFRONTIER Research Infrastructure. This task in now taken over by the INFRAFRONTIER ERIC, which was established by the European Commission in December 2023 with Germany, Czech Republic, Finland, France, Greece, and Sweden as Founding Members. In basic and preclinical biomedical research, the identification of the genetic effects on human disease is a key goal, and the investigation of gene function through appropriate models is a central element in achieving this aim. Here is where the need for an infrastructure like INFRAFRONTIER arises, which, through the operation of the largest mouse repository in Europe, the European Mouse Mutant Archive (https://www.infrafrontier.eu/emma/), offers cryopreservation and distribution of rodent models across and beyond the continent. Moreover, INFRAFRONTIER conducts comprehensive systemic phenotyping of mouse lines and develops new disease models, including germ-free rodent lines intended for gnotobiotic studies and new approach methodologies (NAMs), like in-vitro models. INFRAFRONTIER's service portfolio is continuously expanding, and experts diligently update and curate data on the website to guide academia and industry scientists in selecting the best model to develop groundbreaking therapies. The commitment to excellence and innovation is realised through INFRAFRONTIER's partners; professionals trained in the latest technology and standardised protocols that prioritise animal welfare and drive the 3Rs – replacement, reduction, and refinement – in animal research. INFRAFRONTIER also offers a wide range of courses and training opportunities aimed at researchers and technical staff at any stage of their professional careers. Some examples include workshops on cryopreservation, genetic diseases, and gene editing. INFRAFRONTIER actively collaborates with other Research Infrastructures to enable global access to research data and infrastructures, thereby accelerating the acquisition of knowledge and technological advancements in the field of human health. INFRAFRONTIER also engages with policy makers and funders to align science policy agendas and provide input to societal issues such as animal welfare and the 3Rs.