Lung transplantation is now considered to be a therapeutic option for patients with end-stage lung diseases. Unfortunately, because the problems of lung allograft rejection, it is only a treatment and not a cure. Critical to the continuum of acute to chronic (bronchiolitis obliterans syndrome) lung allograft rejection is a persistent recruitment of peribronchial/vascular leukocytes, eventually leading to an aberrant reparative process and lung dysfunction. The specific mechanisms by which these leukocytes are recruited to the lung allograft have not been elucidated. Chemokines, through their interactions with specific cell surface receptors, selectively mediate the activation and recruitment of phenotypically distinct cells, a process pivotal to rejection. Multiple studies of human lung rejection and translational studies using animal models have demonstrated “proof of concept” that chemokine ligand/receptor biology plays an important role in pathogenesis of acute rejection and bronchiolitis obliterans syndrome.