Kidney transplantation is now accepted to be the best treatment for end-stage renal disease. Despite the improvement of immunosuppressive therapy, there is still actually substantial loss of allografts, in part due to uncontrolled humoral immunity. For many years, the primary technique for the detection of anti-HLA antibodies was the CDC (complement dependent cytotoxicity). The recent use of solid phase assays, mainly the Luminex technology allowed detection of antibodies at much lower levels, and it has been shown that these antibodies have negative impact on the graft survival. We herein review the principal techniques for anti-HLA detection and the different presentations of humoral rejection.