The development of pulmonary infiltrates in an immunocompromised patient remains a difficult diagnostic challenge. The differential diagnosis for pulmonary processes in this population is broad and includes both infectious and noninfectious causes. In addition to bacteria, fungi, viruses, mycobacteria, and protozoa may infect the lung. Similarly, the clinician must consider noninfectious etiologies, such as progression of underlying disease, pulmonary edema, treatment-related toxicity, alveolar hemorrhage, and bronchiolitis obilterans organizing pneumonia. The prognosis for immunosuppressed patients with pulmonary complications is grim, irrespective of the factors leading to the altered immune status. For example, in subjects who require mechanical ventilation (MV) following hematopoietic stem cell transplantation (HSCT), multiple studies1–3 document that mortality rates exceed 80%. Nonetheless, utilization of immunosuppression is expanding, with increasing numbers of both solid-organ transplants and HSCTs performed annually. Similarly, therapies for hematologic malignancies are also becoming more aggressive. Particularly frustrating for physicians who care for these patients is the fact that many of the patients are young and have undergone aggressive interventions in hopes of a cure.