This chapter discusses about the major immune processes of allograft recognition and the methods used to define patient’s immune profile. Cross-match techniques, determination of sensitization against the donor and methods to identify rejection are also described. The major histocompatibility complex (MHC) is a gene cluster located on chromosome 6 which encodes highly polymorphic proteins known as human leukocyte antigens, HLAs. A patient’s HLA profile consists of two sets of alleles which are codominantly expressed; each set, referred to as a haplotype, is inherited from each parent. ABO incompatible transplants have been successfully performed with use of pretransplantation desensitization protocols that involve drugs such as rituximab, splenectomy or plasmapheresis with the aim of reducing circulating antibodies. The measurement of urinary cell granzyme B and perforin mRNA levels, which are indicative of cytotoxic T cell activity, have been found to be sensitive and specific markers for acute T cell-mediated rejection.