Immunocompromised persons are at increased risk for a large group of infections that are either uncommon or much less severe in the immunocompetent host. These opportunistic infections broaden the diagnostic considerations in differential diagnosis of community-acquired pneumonia in patients with immunodeficiencies. This article highlighted epidemiologic factors, clinical presentations, and treatment options for four selected opportunistic infections that represent varied classes of pathogens: nematodes (S stercoralis), mycoses (C neoformans), bacteria (P aeruginosa in patients with HIV infection), and viruses (measles virus).