This article highlights the currently available immunosuppressive medications that are used to prevent or treat hepatic allograft rejection. Currently-available immunosuppressive medications are highly effective in prevention of allograft rejection, graft loss, and patient death. However, side effects of medications are common, usually dose-related, and specific to the administered drug. Maintenance immunosuppression which has been primarily based upon calcineurin inhibitors (Cyclosporine, CsA, or tacrolimus, Tac) is commonly modified to reduce metabolic complications of therapy. Toxic consequences of steroids may be ameliorated by steroid withdrawal without risk of acute rejection or immunologic graft loss. Calcineurin-sparing regimens may include use of mycophenolate mofetil (MMF) or sirolimus, and allow reduction in doses and plasma levels of CsA and Tac. Recurrence of hepatitis C is universal after liver transplantation and progresses rapidly, compared to its natural history in non-immunocompromised patients. Unfortunately, no single immunosuppressive agent or strategy has yet been shown to convincingly modify the course of post-transplant recurrence. Most centers manage recurrenc hepatitis C by either steroid avoidance, reduction in immunosuppression, or institution of antiviral therapy. Ongoing advances in immunosuppressive and antiviral medications will allow tailoring of the immunosuppressive prescription, which undoubtedly will benefit current and future liver recipients.