The standard immunosuppression protocol after liver transplantation (LT) is based on an anticalcineurin (ACN) (tacrolimus or cyclosporine microemulsion) combined with mycophenolate and corticosteroids. Corticosteroids are usually stopped between 6 and 12 months after LT, except for patients whose transplantations were necessitated by autoimmune disease. ACN and mycophenolate must be monitored to verify the dose, with a residual blood assay (for tacrolimus), at 2hours (for cyclosporine microemulsion), or by a simplified area under the curve (for mycophenolate). The first-line treatment for rejection calls for increasing the dosage of tacrolimus (or switching to tacrolimus for patients treated with cyclosporine). Second-line treatment for refractory rejection is corticosteroid bolus (500-1000 mg of methylprednisolone, one to three times). Antibodies blocking the interleukin 2 receptors (basiliximab) or lymphocytes (thymoglobulin) make it possible to reduce the incidence of rejection, decrease corticosteroid doses rapidly and introduce ACN later on (useful in cases of kidney failure). The mTOR inhibitors (sirolimus and everolimus) have different side effects (hyperlipidemia, thrombocytopenia, and pulmonary, cutaneous, and articular events) than ACNs. The absence of any renal or vascular effect is interesting for patients with kidney failure, and the antiproliferative effect can be useful for patients transplanted because of cancer. The current objective of immunosuppression is to reduce the adverse effects (kidney failure, metabolic complications, cancer and infections, in particular, which reduce the survival of patients and grafts), and in the future, to promote the establishment of tolerance that ideally will allow the patient to stop prophylactic immunosuppressant treatment. New chemical agents, capable of acting on new and more specific pathways, are in phase II/III testing.