Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions. Effective immunosuppression in transplantation relies on preventing the immune system from rejecting the allograft while preserving immunologic control of infection and neoplasia. Immunosuppressive regimens include calcineurin inhibitors, anti-metabolites, mTOR inhibitors, steroids and antibody-based therapies. These agents target different sites in the T cell activation cascade, usually by inhibiting T cell activation or via T cell depletion. They are used as induction therapy in the immediate peri- and post-operative period, as long-term maintenance medications to preserve graft function and as salvage therapy for acute rejection in liver transplant recipients. Long-term consequences and side effects of immunosuppression cause more patient morbidity and mortality than is associated with acute rejection.