The European Foundation for the Study of Chronic Liver Failure (EF CLIF) is a private non-profit organization connecting biomedical researchers and healthcare professionals with each other, with patients and patient associations, and with society. The fundamental purpose of EF CLIF, reflected in its founding Statements of 2015, is to advance knowledge and promote research and education in liver disease to improve the prognosis of patients living with chronic liver failure. The Foundation has made pioneering efforts in conducting a series of large, international prospective studies that have been instrumental in reclassifying the trajectory of patients with chronic liver failure and led to the clinical, prognostic and pathophysiological definition of the syndrome referred to as “acute-on-chronic liver failure” characterized by acute decompensation of cirrhosis, severe systemic inflammation, organ failures, and high short-term mortality. We are inspiring best clinical practices for the management of patients with chronic liver failure and promoting a more sustainable and equitable healthcare system. Within the Foundation, the European Association for the Study of the Liver (EASL) Chair supports research activities through the EASL-CLIF Consortium, a network of 117 tertiary care and university hospitals in 28 European countries. The Grifols Chair promotes translational studies in centers across Europe and North America within the framework of the European Network for Translational Research (ENTR) with 25 centers in 8 countries. Over the last five years, the Foundation has successfully expanded its geographical scope providing the context to support transcontinental collaborative research projects. The Global Projects chapter provides the framework to promote research in cirrhosis across the world with the aim to help to build consensus and ensure health equity worldwide.