Immunosuppression for renal transplantation has undergone more changes over the last 8 years than at any other time in its history. It is now possible to be more selective in the matching of drugs with a given patient. This brings with it the option of improving graft outcome and also minimizing adverse effects. It is an ongoing process that will utilize agents working at different points in the activation cascade of the CD4+ ‘helper’ T lymphocyte. It may also be possible to manipulate the immune system such that the organ-specific immune response may be switched off, or rendered ‘tolerant’, thus removing the need for any immunosuppressive drugs. In this brief review, we shall address each of these approaches and discuss other therapeutic avenues being investigated.