Liver transplantation (LT) in the United States is evolving in response to shifting disease patterns, innovative therapies, and technological advancements. Metabolic-associated fatty liver disease (MAFLD) and alcohol-associated liver disease (ALD) now are the most common indications for LT, reflecting the impact of the obesity epidemic and increased alcohol consumption. Advances in pharmacotherapy for MAFLD and tailored protocols for ALD management are reducing disease progression and improving outcomes. The inclusion of colorectal liver metastases (CRLM) and intrahepatic cholangiocarcinoma (iCCA) as transplant indications highlights progress in chemotherapy and patient selection. Technologies like normothermic machine perfusion (NMP) are expanding the donor pool, while xenotransplantation and organ rehabilitation offer transformative solutions to organ shortages. As the population ages, LT programs must address challenges in older patients and explore minimally invasive approaches for donors and recipients. By integrating innovation and multidisciplinary expertise, LT will continue to provide life-saving care while adapting to the needs of diverse patient populations.