Ischemia-reperfusion, surgical injury, and bacterial translocation trigger the innate immune system, starting acute rejection. Interaction between donor and recipient immune cells generate injury and tolerance, which occur mostly in secondary lymphoid organs, lamina propria, and epithelium. Chronic rejection mostly affects the endothelial cells, generating graft dysfunction. DSA increase the risk of graft rejection both acutely and chronically, and the liver protects against their effects. Induction therapies deplete lymphocytes prior to implantation, and maintenance therapies inhibit T-cell expansion. Rejection rates are the lowest when depleting drugs and a combination of interleukin 2 receptor blockade, inhibition of T-cell expansion, and steroids are used as maintenance therapy. Chimerism and tolerogenic regiments that induce Tregs and prevent the development of DSA are important treatment goals for the future.