Cytomegalovirus (CMV) pneumonia is a major cause of morbidity and mortality in allogeneic bone marrow transplant and lung transplant recipients. However, its role as a cause of lung disease in patients with the human immunodeficiency virus (HIV) is controversial. Although CMV can be isolated from lung specimens in patients with HIV-associated respiratory illness, it is rarely the causative pathogen. Most adults with HIV infection have latent CMV infection of many tissues including the lung, and most cases of CMV pneumonia are believed to be caused by reactivation secondary to severe immunocompromise. The clinical presentation of pneumonia caused by CMV pneumonia is similar to that of Pneumocystis carinii, with fever, cough, hypoxemia, and diffuse radiographic opacities. Although the two infections can not be differentiated on clinical grounds alone, the presence of extrapulmonary CMV disease and the use of recent cytotoxic chemotherapy or corticosteroids suggests the diagnosis of CMV pneumonia. Although approximately 60% of cases respond initially to anti-CMV therapy, the disease is associated with progression and high early mortality, probably related to severe underlying immunosuppression.