Pneumocystis is an opportunistic fungus that is a major cause of morbidity and mortality in immunocompromised hosts. Despite a decline in incidence with the advent of highly active antiretroviral therapy (HAART), Pneumocystis remains the most common opportunistic infection in patients with the acquired immunodeficiency syndrome (AIDS) and is an increasing cause of disease in patients with other forms of immunosuppression. Although there have been advances in the prevention and treatment of this infection, the mortality for Pneumocystis pneumonia (PCP) in the setting of AIDS remains 10 to 20%. The mortality for patients with other forms of immunosuppression is poorly defined but may actually be higher than that reported in the setting of AIDS. The continued severity of PCP in the AIDS population, its increasing frequency in other immunosuppressed populations, and increasing evidence that normal hosts may serve as a reservoir for the organism merit continued evaluation of the epidemiology, clinical presentation, diagnosis, and treatment of this infection.