Orthotopic liver transplant is the only cure for end stage liver disease. Enormous progress has been made in the fields of graft and patient survival since the introduction of cyclosporine and tacrolimus. Scientists involved in basic and clinical research have dedicated their efforts to understanding the mechanisms of action and the side effects of these medications with the goal of finding the perfect balance between the well-being of the patient and the avoidance of rejection. A great deal of work has been done and now we can propose a variety of treatments suitable to different clinical scenarios. The introduction of new medications will offer even more options for the treatment of rejection in liver transplant patients.