Orthotopic liver transplantation (OLT) recipients have been reported to have decreased perioperative opioid and intraoperative inhalational anesthetic requirements when compared to patients without liver disease undergoing other types of major abdominal surgeries. The severity of the liver disease and the process of the transplantation itself may alter the pharmacokinetic and pharmacodynamic effects of different pain medications. Chemical injury of the liver and the high degree of surgical stress may also increase the levels of neuropeptides involved in pain modulation. Per the U.S. Department of Health and Human Services Organ Procurement and Transplantation Network, more than 5,000 OLT cases are being done per year since 2000. With better understanding of the pathophysiology of liver disease and the development of perioperative anesthesia management, the recent concept of improving patient outcome following OLT includes a fast-track approach in selected patients, which may shorten or completely bypass intensive care unit stay and reduce costs. With this development, the understanding of the analgesic pharmacology in the care of the OLT patients is even more important. Proper dosage of medications can achieve adequate intraoperative anesthetic depth and postoperative pain control, while avoiding over-sedation which increases risk of prolonged postoperative mechanical ventilation. The purpose of this review is to summarize the pharmacokinetics and pharmacodynamics of the analgesic medications commonly administered to this patient population.