Lung transplantation has come of age and is now considered a valid treatment for selected patients with end-stage lung disease. In recent years, survival rates have much improved, although the development of chronic rejection, characterized by a progressive and irreversible decline in FEV(1), which is clinically defined as bronchiolitis obliterans syndrome (BOS) remains the major obstacle to long-term survival. Extensive research efforts with special emphasis on innate immunity have recently led to new insights with the identification of at least two different phenotypes: on the one hand there is an azithromycin-responsive phenotype (the so-called neutrophilic reversible allograft/airways dysfunction (NRAD), on the other hand there is an azithromycin-unresponsive phenotype (the fibroproliferative form of BOS or classical obliterative bronchiolitis). The present review intends to give the scientific evidence for these two subtypes, and to clarify the role of azithromycin in the treatment of BOS.