Pulmonary complications are a significant cause of early mortality (up to 100 days) after hematopoietic stem cell transplantation (HSCT). While infectious complications particularly due to opportunistic pathogens are common in these patients, diffuse lung injury is a non-infectious complication occurring in 25-50% of HSCT recipients. The incidence of this complication is higher with allogeneic as apposed to autologous transplants and is largely dependant on the method of graft versus host prophylaxis. The spectrum includes interstitial pneumonitis (IP), bronchiolitis obliterans (BO), diffuse alveolar hemorrhage (DAH) and noncardiogenic capillary leak syndrome (NCLS). In 1993 a panel convened by the National Institutes of Health (NIH) defined widespread alveolar injury following HSCT that occurs in the absence of an active lower respiratory tract infection and cardiogenic causes as the idiopathic pneumonia syndrome (IPS). IPS is a clinical syndrome with variable histopathologic correlates and several potential etiologies. Peri-engraftment respiratory distress syndrome (PERDS) and delayed pulmonary toxicity syndrome (DPTS) are also included within the definition of IPS. Histopathologic findings associated with IPS include diffuse alveolar damage with hyaline membranes, lymphocytic bronchitis and bronchiolitis obliterans organizing pneumonia (BOOP). The pathophysiology involves four distinct mechanisms, namely: the toxic effects of chemotherapy, immune dysregulation, alloreactive donor cells and host cell responses. The roles of lipopolysaccharide (LPS), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor (TNF) in the genesis of endothelial cell injury are being defined. Therapy for IPS includes supportive care and immunosuppressive agents. The role of TNF antagonists is being studied in ongoing clinical trials.