The success of transplantation with good long-term outcome is closely related to the possibilities of iatrogenic immunosuppression. Progress in immunosuppression combines basic scientific research of alloimmunity with practical clinical management of transplanted patients, their underlying diseases, and management of immunosuppressant side effects. Calcineurin inhibitors and steroids form the basis of immunosuppression in liver transplantation. To prevent steroid side effects and most importantly nephrotoxicity, the roles of antimetabolites such as mycophenolate and calcineurin inhibitor reduction have become more important. Developments in the 1990s provided specific antibodies and induction protocols renabling the delayed application of calcineurin inhibitors and a reduction in side effects. Against the background of a range of indications reaching from chronic viral infection to tumors, the progress of immunosuppression is characterized by the calculated combination of synergistic individual immunosuppressants. Novel drugs and strategies for the induction of tolerance are under development.