Despite marked improvements in early survival, long-term outcome after lung transplantation is still threatened by obliterative bronchiolitis (OB). Thought to be a manifestation of chronic allograft rejection, OB affects up to 65% of patients at 5 years after surgery and produces a relentless airflow obstruction. Early and late acute rejection are the primary risk factors for OB, but cytomegalovirus infection and airway ischemia may also play a role. In most patients, OB responds poorly to augmented immunosuppression and eventually leads to infectious complications and terminal respiratory failure. Because early diagnosis is associated with better prognosis, every effort should be made to detect OB in a preclinical stage. This may be best achieved by combining several techniques, such as surveillance transbronchial biopsy and bronchoalveolar lavage, measurements of ventilation distribution and exhaled nitric oxide, and expiratory computed tomography.