Over the past 15 years, lung transplantation has become an established treatment for a variety of end-stage lung diseases, but medium- and long-term success has been limited by a high incidence of bronchiolitis obliterans syndrome (BOS). Immune mediated injury has been recognized as the leading cause of BOS, and the term is synonymous with chronic rejection. But recently, nonimmune mechanisms, such as gastroesophageal reflux, have been recognized as potential culprits. The results of various treatment options have generally been disappointing, and BOS has emerged as the leading cause of late morbidity and mortality after lung transplantation.