Pneumocystis pneumonia (PcP) in humans is caused by Pneumocystis jirovecii, which has recently been reclassified as a fungus because its cell wall composition and nucleotide sequences are more similar to those of fungi. PcP occurs only in immunocompromised individuals such as those with AIDS. Despite the use of highly active antiretroviral therapy, PcP remains the leading opportunistic infection in AIDS patients. Based on nucleotide sequence variations in the internal transcribed spacer region of rRNA genes, more than 60 different types of P. jirovecii have been identified. Although type differences do not appear to correlate with the clinical characteristics of PcP, nucleotide sequence variations of the organism have been useful in epidemiologic studies. As a result, some recurrent infections are found to be due to re-infection with new types, and outbreaks due to the same types of P. jirovecii have been identified. Initial diagnosis of PcP is usually based on symptoms and chest radiography. A characteristic histopathologic feature is the presence of acellular eosinophilic exudates and organisms in the alveoli. Ultimate diagnosis of PcP is achieved by demonstration of the organism in induced sputum or bronchoalveolar lavage fluid by tinctorial staining or polymerase chain reaction (PCR). Among the many different PCR methods, the nested PCR that targets the large subunit mitochondrial rRNA gene is the most sensitive and specific. Combination of trimethoprim and sulfamethoxazole is the first choice of drugs for both treatment and prophylaxis of PcP. Other drugs that can be used include a combination of primaquine and clindamycin, pentamidine, atovaquone, and a combination of dapsone and trimethoprim. Pneumocystis organisms have the ability to inactivate the phagocytic activity of alveolar macrophages and to induce them to undergo apoptosis. This apoptosis is due to activation of caspase 9 by polyamines that are present in high levels in the lung and alveolar macrophages during PcP.