Purpose:The clinical success of human lung transplantation is limited by the development of bronchiolitis obliterans syndrome, a pulmonary specific manifestation of chronic allograft rejection. Although the etiology of bronchiolitis obliterans syndrome is not well understood, there is increasing evidence for a role of antibody to human leukocyte antigens in the development of this condition. This review critically evaluates recent publications that have investigated the clinical significance of anti human leukocyte antigen antibody in lung transplant recipients.Recent findings:A striking association has been observed between the development of antibody to donor human leukocyte antigen and bronchiolitis obliterans syndrome in some lung transplant patients. Indirect presentation of donor human leukocyte antigen may be critical to the development of anti human leukocyte antigen antibody. In human airway epithelia culturedin vitro,anti human leukocyte antigen antibody‐ligand interactions induce fibroproliferative and apoptotic responses, implying a mechanistic role for antibody in the development of bronchiolitis obliterans syndrome.Summary:The response to allogenic solid organ transplant appears complex, involving both cellular and humoral components. Emerging evidence supports a pathogenic role for antibody to donor human leukocyte antigen in the development of chronic lung transplant rejection. Additional research is needed to better understand mechanisms of antibody production, further describe cellular effects of antibody‐ligand interactions, and, importantly, explain why anti human leukocyte antigen antibody is detectable in only a subset of patients with bronchiolitis obliterans syndrome.