Obliterative bronchiolitis (OB) has emerged as the main cause of morbidity and mortality in the long-term follow-up after lung and heart-lung transplantation. The pathogenesis of OB is multifactorial, with acute rejection and cytomegalovirus infection being the main risk factors for the development of OB. The final common pathway of all inciting events seems to be an alloimmune injury, with subsequent release of immunologic medicators and production of growth factors leading to luminal obliteration and fibrous scarring of the small airways. Analyzing the 14 years of experience in 163 patients at Stanford University, we found a current incidence of bronchiolitis obliterans syndrome or histologically proven OB within the first 3 years after lung and heartlung transplantation of 36.3%, with an overall prevalence of 58.1% after heart-lung and 51.4% after lung transplantation. Both pulmonary function indices (forced experiratory flow between 25% and 75% of forced vital capacity and forced expiratory volume in 1 second) and transbronchial biopsies have proven helpful in diagnosing bronchiolitis obliterans syndrome or OB at an early stage. Early diagnosis of OB and improved management have achieved survival rates in patients with OB after 1, 3, 5, and 10 years of 83%, 66%, 46%, and 22%, compared with 86%, 83%, 67%, and 67% in patients without OB. Recently, different experimental models have been developed to investigate the cellular and molecular events leading to OB and to evaluate new treatment strategies for this complication, which current limits the long-term success of heart-lung and lung transplantation. © 1995 The Society of Thoracic Surgeons.