Lung transplantation is a therapeutic option for patients with end stage lung diseases, but long-term survival remains poor, primarily due to chronic allograft rejection. Bronchiolitis obliterans (BO), a fibrotic process resulting in progressive narrowing of bronchiolar lumens and airflow obstruction, is a manifestation of chronic allograft rejection. The term obliterative bronchiolitis ( OB) is synonymous. Once bronchiolitis obliterans syndrome (BOS) develops, progressive decline in pulmonary function is typical; most patients die of respiratory failure within 5 years of onset. The diagnosis of BOS is usually made by clinical, physiological, and radiographic parameters. The dominant risk factor for BOS is acute allograft rejection, but additional factors play contributory roles [e.g., infections; human leukocyte antigen (HLA) mismatching; and injury to the allograft or airways]. The pathogenesis of BOS is complex and involves myriad cell types (both immune and nonimmune) and release of diverse cytokines and chemokines. Unfortunately, current therapies for BOS are of unproven value. A greater understanding of the pathogenic mechanisms operative in BOS are critical to developing novel strategies to treat and prevent this devastating complication.