The first liver transplantation (LT) was conducted in 1963. After a two-decade development phase with the improvement of surgical and anesthesia-resuscitation techniques, and a better control of allograft rejection, LT has become the benchmark treatment for the majority of end-stage liver diseases. Since the 1980s, indications of LT have gradually expanded and the current main indications in adults are hepatocellular carcinoma at an early stage (15 to 30% of indications), C cirrhosis (15 to 40% of indications) and alcoholic cirrhosis (20 to 25% of indications). Five thousand LTs are performed yearly in Europe, including 1000 LTs in France, with, over the 2000-2006 period, survival rates of 86, 75 and 68% at one, five and 10 years, respectively. Several advances have accompanied the increasing number of indications and these excellent results: (a) the development of more specific immunosuppressive drugs to prevent rejection, the incidence of which is currently less than 20%: tacrolimus, mycophenolic acid, anti-IL2 receptor antibodies, mTOR inhibitors, (b) a policy of active recruitment of organs together with surgical innovations (split liver, domino LT, living donor transplantation) contributing to the expansion of the pool of organs, (c) standardization of organ allocation policies, based on the sickest first policy. The applicability of LT, however, remains limited by the shortage of organs and the occurrence of long-term complications of immunosuppression. Due to the lack of effective alternative perspectives to LT for the treatment of end-stage liver diseases, the two major challenges for the liver transplant community should be the optimization of organ recruitment and the development of innovative immunosuppressive regimens able to overcome the side effects of current immunosuppressive drugs. The development of non heart beating donation and appropriate use of intrafamilial donation could partly compensate for the organ shortage in the midterm. The identification of molecular signatures in tolerant patients in whom immunosuppression could be stopped, and induction of tolerance, trough lymphocyte depletion or T lymphocyte costimulation blockade, are the most advanced research ways to reduce complications of immunosuppression.