Transplantation of solid organs is the treatment of choice for most patients with end-stage organ diseases. In the absence of pharmacological immunosuppression, recognition of foreign (allogeneic) histocompatibility proteins expressed on donor cells by the recipient's immune system results in rejection of the transplanted tissue(s). One-year renal transplant survival is now routinely over 90% in most centres, largely the result of improvements in immunosuppressive drugs. In this article, we review commonly used immunosuppressive medications and discuss their pharmacological modes of action. Given that long-term graft outcomes remain poor despite improvements in early transplant survival, we discuss, in addition, novel experimental strategies for the induction of tolerance to transplanted tissues that have translational relevance to human organ recipients.

Key Concepts:

• The major limitation of solid organ transplantation is long-term immunosuppression which either results in excessive mortality and morbidity or is insufficient to prevent chronic rejection of transplanted tissues.
  
• An understanding of transplant rejection and pharmacological targets of immunosuppression is key to devising novel strategies of preventing rejection by inducing transplant tolerance.