With few exceptions, pulmonary complications in the immunocompromised host will proceed to death unless the clinician intercedes. The differential diagnosis of diffuse pulmonary disease in this setting includes (1) infection, most commonly from opportunistic organisms; (2) recurrence or extension of the basic underlying disease process to involve the lungs; (3) adverse pulmonary reaction to drugs; (4) a new, unrelated disease process such as cardiac pulmonary edema or pulmonary emboli; and (5) any combination of these categories. Up to a third of these patients have two or more complications, such as pneumonitis from two different opportunistic organisms or an opportunistic infection and a drug-induced pulmonary complication. An understanding of the host defense that is compromised enables the clinician to narrow the differential diagnosis. The most common types of impairment of defense mechanisms are reductions in the number of granulocytes, B-lymphocytes, or T-lymphocytes, and not uncommonly, two or all three of these types of cells are involved. Impairment of each of these cell types is associated with an increased frequency of infection by a particular group of organisms. Consequently, the clinician can be somewhat selective if empiric therapy is being considered. In the immunocompromised patient, most pulmonary complications, including drug-induced pulmonary disease and pulmonary emboli, are associated with fever that mimics an infection. Up to 25% of the pulmonary complications in these patients are noninfectious.