Recent advances in immunosuppressive drug regimens have changed the outcome after liver transplantation significantly in the last two decades. However, chronic rejection and long-term graft survival remains a major problem. Side effects like drug-induced nephrotoxicity, hypertension, osteoporosis, hyperlipidaemia and neuropathy of some immunosuppressive agents play an essential role in long-term allograft and patient survival. This review outlines the current treatment of short- and long-term immunosuppression in liver transplanted patients, it summarizes the treatment of acute and chronic rejection, describes the complications and side effects of immunosuppressive therapy and points out the current use of immunosuppressive therapy in living-related liver transplantation.