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Major advancements have been made in the past decade with regard to immunosuppressive therapy in liver transplant recipients. Experimental and clinical evidence suggests that the liver is an immunologically privileged organ, and an episode of acute rejection does not appear to have a negative impact on patient or graft survival. Today, the most pressing issue related to immunosuppression therapy in liver transplantation is minimizing toxicity, the incidence and severity of recurrent disease, and avoiding cardiovascular and cancer risk. Studies have identified a number of factors that have been associated with acute rejection, and similarly a number of factors have been associated with an increased risk of and severity of recurrent disease. Therefore, tailoring immunosuppression to the individual patient should become more popular, particular as it relates to patients with hepatitis C virus. This review aims to highlight the evolving trends in immunosuppressive therapy in liver transplantation.