Human leukocyte antigen (HLA) antibody-mediated hyperacute rejection has dramatically decreased since the clinical introduction of crossmatch technology. However, the role of HLA antibody in acute and chronic rejection remains unclear. In this article, we cite publications to show the correlation between HLA antibody and allograft rejection. Potential pathological mechanisms of antibody-mediated rejection are also proposed and the rationale of commonly used HLA antibody detection techniques are introduced. The advantages and disadvantages of these technologies are further discussed in detail. We conclude that owing to the recent availability of improved antibody detection methods, a causal relationship between HLA antibodies and allograft rejection is now considered to exist.