The tremendous success of OLT as a highly effective treatment for patients with end-stage liver disease has resulted in a rapid increase in the number of candidates for the procedure. Refinements in organ preservation, improvements in surgical technique and immunosuppression, and better postoperative management have contributed to improved survival rates. The discrepancy between the paucity of organs and the increasing numbers of potential recipients will continue to worsen until there are extraordinary breakthroughs in providing alternatives to human whole-organ livers, such as xenografts or cultured hepatocyte infusions. For now, the vast majority of patients with life-threatening liver disease are not likely to receive a liver graft. Thus, the issues of patient selection and timing of OLT have become even more relevant. Prompt referral to a transplant center is not only in the patient's best interest, but also it has been shown to be cost-effective. Over the last 30 years, it has become clear that hepatic malignancy, initially a common reason for OLT, should be an indication for transplantation only in highly selected individuals. The role of adjuvant chemotherapy needs to be defined, and proven treatment alternatives need to be developed. New antiviral agents may enable a large group of patients with chronic hepatitis B to be successfully transplanted, placing even greater demands on the already limited supply of donor livers. Hepatitis B appears to be species specific, and it is conceivable that xenotransplantation from a nonsusceptible donor species may confer protection to HBV reinfection, eliminating the problems of an inadequate donor supply. Until novel approaches, including xenotransplantation, gene therapy, or replacement of hepatic function by cultured hepatocyte infusions, become a widespread reality, future allocation policies may highlight outcome as well as urgency as a fundamental variable to determine if transplantation is reasonable. Survival rates have been shown to fall with advancing levels of urgency, resulting in a conflict between equity and efficacy in organ allocation. As waiting lists for liver transplantation continue to grow, it is becoming increasingly apparent that patients must be referred to a transplant center earlier in the course of liver disease.