Although the transplanted human liver is susceptible to rejection with a similar incidence of rejection as seen with renal allografts, the liver enjoys many immunological benefits relative to other transplanted organs. These include relative resistance to antibody-mediated injury, low frequency of chronic rejection, relatively easy reversibility of acute rejection, and even reversibility of chronic rejection. The reasons for the liver's favored status from an immunological perspective are unclear but are perhaps multifactorial. Currently used clinical protocols of immunosuppression for liver transplantation rely principally on the calcineurin inhibitors, cyclosporine and FK-506. Steroid withdrawal at variable periods after liver transplantation is becoming increasingly common. Compared with other organ transplants, relatively few human liver transplants are lost because of rejection. The transplanted liver may be an appropriate target for tolerance studies.