After organ transplantation an immunosuppressive regimen is required to prevent graft rejection. Immunosuppressive drugs inhibit immune function by targeting both T- and B-cell responses through blockage of cellular proliferation induced by alloantigen stimulation, and by inhibition of the cytokine production necessary for such stimulation. However, the absence of discrimination between the immune response against alloantigen from the transplanted organ and the immune response against environmental antigens renders transplanted patients strongly immunodeficient and susceptible to bacterial and viral infection. Optimising the immunosuppressive drug regimen to balance mandatory immunosuppression while preserving immunity is a difficult challenge for clinicians in charge of transplanted patients. The development and optimisation of assays to monitor the current state of an immune response is of great interest. This article reviews the mechanisms of the alloimmune response against the transplanted organ and the consequences of immunosuppression for the patient's immunity. The development and optimisation of assays for monitoring the current status of the immune response after organ transplantation is discussed, as are novel therapeutic approaches based on induction of tolerance and cellular therapy.