Despite the impressive results of one-year survival rates, organ transplantation still faces major problems. Current anti-rejection drugs reduce systemic immunity nonselectively and increase the risk of infection and cancer on the long term. Theoretically, selective inhibition of alloimmune response can be achieved at the organ level by intragraft transfer of genes with immunomodulatory properties. In the last decade, gene therapy emerged as a new strategy in renal, heart and liver transplantation, showing promising results in experimental animals, almost in controlling acute rejection. The success of gene therapy in the transplant medicine is strongly dependent on the efficiency of the delivery system that allows local transfer and expression of the therapeutic gene in the target organ or tissue. The main findings concerning the suitability of gene therapy in preventing graft rejection will be discussed here.