Liver transplantation has enjoyed increasing success in the last decade. It has emerged from an experimental stage to become the mainstay of treatment for end-stage liver disease, with more than 4000 transplants performed annually (1–3). Despite the success of liver transplantation, rejection, infection, donor availability, and poor immediate graft function present persistent problems and contribute to mortality rates in the range of 15–25% within 1–2 years after surgery (1, 3, 4). Every liver is damaged to some extent during the transplantation process, but some livers are so severely injured that they are unable to sustain life (primary nonfunction) and, often, must be immediately retransplanted. Others show borderline function (primary dysfunction), for which patients often require prolonged treatment in the intensive care unit. The development of University of Wisconsin cold preservation solution (5) has provided a major advance in liver transplantation. Preservation injury is slowed 2–4 times using UW solution compared with previously used preservation solutions (6, 7). Thus, posttransplantation liver function has been improved and viable storage time of the liver has been extended up to 24–30 hr, thereby significantly increasing organ availability and sharing (8). Nevertheless, preservation injury continues to be a serious problem. Primary nonfunction still occurs at an unacceptable rate ranging between 2 and 23% and is a major cause of death in transplantation (8–11). Additionally, there is clinical evidence that severe preservation injury is associated with an increase in liver graft rejection (12). In order to reduce the rate of primary nonfunction and dysfunction, it will be important to understand the mechanisms underlying liver injury during storage and reperfusion. Significant advances have been made in this area over the past few years. The purpose of this review is to detail these advances and to present them in a framework that seems to fit a partic-ular set of liver injuries, one of which is preservation injury. These injuries involve both sinusoidal lining cells (SLC)* and