In this review of current publications, we look at the molecular mechanisms of tolerance of the liver and its allografts in terms of minimization and possibilities of withdrawing immunosuppressive therapy, mainly in the long-term period after liver transplantation. Information about clinical trials with regulatory T cells (Tregs) for the purpose of tolerance induction is presented. Data from a new consensus study on individualization of immunosuppressive therapy regimens are presented. Options for possible withdrawal of immunosuppression both in the early and in the long term after liver transplantation (LT) are considered. We suggest a way to study the lymphoproliferative potential of a liver transplant recipient to be investigated, since not only rejection determines life expectancy, but also the degree of immunosuppression effect on bone marrow depending on patient age.