Pancreas transplantation represents one of the most technically challenging solid organ transplant procedures, demanding specialized anesthetic expertise. This chapter provides a comprehensive overview of anesthetic considerations for pancreas transplantation, addressing unique challenges in recipients with long-standing diabetes and significant end-organ complications. Preoperative evaluation requires a thorough cardiovascular and autonomic neuropathy assessment, given the increased perioperative risk. Intraoperative management focuses on maintaining hemodynamic stability during reperfusion syndrome, when hypotension, bradycardia, and metabolic derangements commonly occur. Critical aspects include goal-directed fluid therapy, glycemic control, coagulation management, and temperature maintenance. The chapter addresses simultaneous pancreas–kidney transplantation (80% of cases) and emerging islet cell transplantation techniques. Postoperative care emphasizes graft perfusion optimization and multimodal pain management. Current outcomes demonstrate 1-year graft survival rates of 86% for simultaneous procedures. The role of anesthesiologists is crucial in this multidisciplinary approach, directly impacting patient and graft outcomes.