During this formative period, liver transplantation transitioned from animal experiments to the first human orthotopic grafts, catalyzing rapid advances in surgical technique, graft perfusion, and postoperative care. Research emphasized feasibility and translational pathways, anchored by early case reports and foundational studies of graft vascularization from animal models to humans. A central thread was the emergence of graft rejection as a major challenge, driving early immunosuppressive experimentation and the exploration of retransplantation and regenerative biology to support graft viability. Widespread use of canine models and early xenotransplant concepts provided the experimental substrate for testing graft survival and immunologic responses, while studies of liver circulation and donor management framed selection and monitoring strategies. Historical Significance: The era established the feasibility of clinical liver transplantation and set the stage for surgical standardization, donor evaluation, and long-term immunosuppression. Foundational anatomical and physiological insights into hepatic vascularization informed graft integration and organ perfusion, underpinning subsequent improvements in outcomes and indications. The period's cross-species comparisons and early xenotransplant ideas laid essential groundwork for understanding immune rejection and guided the trajectory of later transplantation science.