The gold standard treatment of end-stage liver disease continues to be liver transplantation (LT). The challenges of LT require skilled anesthesiologists to anticipate physiologic changes associated with end-stage liver disease (ESLD) as well as surgical considerations that affect multiple organ systems. While on the waiting list, patients may be placed new anticoagulation medications that can confound already complex coagulopathy in LT patients. Pain management is often an afterthought for such a complex procedure but appropriate medications can help control pain while limiting opioid medications. Surgical stress and medications for immunosuppression can affect perioperative glucose management in ways that have implications for patient and graft survival. 2020 provided a new challenge for anesthesiologist, the COVID-19 pandemic. The uncertainty of the novel respiratory virus challenged providers in beyond just LT patients.