Bronchiolitis obliterans syndrome (BOS) is the leading cause of death in lung transplant recipients (LTR). BOS is thought to result from chronic immunologic/inflammatory insults leading to peri-bronchiolar leukocyte infiltration, with a subsequent exuberant tissue re-modelling and fibro-obliteration of the luminal space of the allograft airways. Diagnosis is based on functional criteria and severity is graded on the degree of Forced Expiratory Volume in 1 second (FEV1) impairment. Current strategies to improve pulmonary function once BOS is established have demonstrated little or no impact on disease progression and re-transplantation remains the only therapeutic option. Among the alternative treatments which have been attempted in the last few years, long-term azithromycin treatment seems to be the most promising therapeutic device for BOS treatment. Azithromycin is a macrolide antibiotic, endowed with a broad spectrum of anti-inflammatory/immunomodulatory activities. Long-term oral azithromycin therapy can significantly improve FEV1 in about 42% of patients with established BOS. Moreover, reduced neutrophilia, chemokine release and bacterial exacerbations have been demonstrated. These observations suggest that the drug can down-regulate pulmonary inflammation, even if the precise underlying mechanisms still need to be determined.