Research into the possibility of liver transplantation (LT) started before the 1960s with the pivotal baseline work of Thomas Starzl in Chicago and Boston, where the initial LT techniques were researched in dogs. Starzl attempted the first human LT in 1963 in Denver, but a successful LT was not achieved until 1967. In 1970, with an immunosuppressive regimen largely based on steroids and azathioprine, survival rates were dismal—approximately 15% at 1-year follow-up. LT did not become a clinical reality until the early 1980s, after the discovery of cyclosporine, which led to improvements in rejection rates. In 1983, the US National Institutes of Health established, by consensus, that LT was to be considered out of the experimental realm and was to be clinically accepted as definitive therapy for end-stage liver disease (ESLD). Additional improvements in immunosuppression that were instrumental in advancing the science included the discovery of monoclonal antibodies (ie, muromonab-CD3 [OKT3]) in 1986. The combination of improvements in rejection rates and in surgical technique led to an enormous growth of the field during the 1980s, with expansion from 3 centers in 1982 to more than 120 centers today. In 2017, over 8,000 procedures were performed, up from approximately 100 in 1982. Of great importance in this expansion was the development of the University of Wisconsin (UW) solution in 1988, which increased preservation time and allowed for a smoother surgical procedure, avoiding a rushed tour de force in the operating room. Finally, the development of newer immunosuppressants, such as tacrolimus and interleukin-2 (IL-2) receptor blockers, has paved the way for further growth in this field. All those advances have produced excellent results, with current 1-year patient survival rates of 91-93% and 5-year survival rates of 75-84%. [1] Future advances may include the development of xenotransplantation, which was pioneered by Starzl in 1992, and the development of cloning techniques and their impact on organ availability. Organ allocation has also evolved over time, with the current system based on the Model for End-Stage Liver Disease (MELD; see the MELD Score calculator), with a focus on maximizing transplant benefit. [7, 8] Further refinements of the model are always ongoing and aim to improve fairness in allocation and survival results. Hepatitis C virus, hepatocellular carcinoma (HCC), chronic kidney disease, and alcohol abuse relapse continue to be major challenges, and continued research in these areas will undoubtedly lead to better outcomes for transplant recipients.