Transplantation is the most definitive and effective treatment for end-organ failure. Over the past few decades, innovation in surgical techniques, mechanical circulatory support, allograft preservation methods, immunopharmacology, and anesthetic management have markedly improved transplant outcomes (Deschenes, Liver Transpl 19(Suppl 2):S6–S8, 2013; First, Transplantation 53(1):1–11, 1992; Wilson et al, Anesth Analg 139(6):1267–1282, 2024). Challenges for all types of transplantation remain, however, including increased global demand, allograft shortages, and longer waitlists (Jadlowiec, Taner, World J Gastroenterol 22(18):4438–4445, 2016; Cypel, Keshavjee, Thorac Surg Clin 25(1):27–33, 2015). To combat these challenges, living donation has increased for kidney and liver transplantation. The deceased donor pool for all transplants has also expanded to include higher-risk donors and more marginal allografts (Jadlowiec, Taner, World J Gastroenterol 22(18):4438–4445, 2016). Higher-risk donors, known as extended-criteria donors, may have advanced age, prolonged intensive care unit stays, electrolyte abnormalities, hemodynamic instability with high vasopressor requirements, and certain infections, such as hepatitis C infection (Wilson et al, Anesth Analg 139(6):1267–1282, 2024). Marginal allografts may have high adipose content, exposure to a prolonged ischemia time, or come from donors who underwent donation after circulatory death (Wilson et al, Anesth Analg 139(6):1267–1282, 2024). New research and innovations are thus needed to continue to expand the donor pool, minimize the risk of postoperative graft dysfunction and rejection, and improve overall postoperative transplant outcomes. This chapter will explore advances and future directions in regional anesthesia, organ preservation technology, and xenotransplantation.