Three main aspects of rejection are described in kidney transplantation: hyperacute graft rejection mediated by cytotoxic antibodies, acute rejection initiated by lymphocytes T CD4+ activated after direct or indirect pathways of allopeptides recognition, and chronic rejection (graft chronic dysfunction). Immunologic and non-immunologic factors have been implicated in the development of chronic rejection but there is no evidence for a unique physiopathological pathway. The various steps of immune response in acute rejection have been better defined in the past years. The development of new immunosuppressive drugs and their combination have led to drastic decrease of acute graft rejection occurrence. On the other hand, highly HLA sensitized recipients, chronic graft rejection and toxicity of immunosuppressive drugs should support active research but the final goal is the induction of a specific tolerance.