This chapter emphasizes on the importance of suppression of alloimmune response for successful organ transplantation. The foreign antigens are presented either by the foreign cells or tissue of the donor or by the leukocytes of the recipient. The immunocompetent cells destroy the foreign cells. An inflammatory response involving monocytes and macrophages participates in this alloimmune response. Two pathways of allorecognition, direct and indirect, contribute to donor antigen (allograft) rejection. To prevent allograft rejection, pharmacological immune prophylaxis, continuous immune and allograft function monitoring, and, if necessary, an augmentation of immunosuppression must be conducted. The chapter discusses rejection management, which includes rejection diagnosis, induction therapy, glucocorticoid withdrawal, and sensitization therapy. Only true "immunologic" tolerance can provide the outcome pursued-namely, prolonged allograft function and otherwise normal immune function, without chronic immunosuppressive therapy and its risks. Until a successful tolerance-inducing protocol is developed, the current and upcoming immunosuppressive agents and techniques must be used.