Immunocompromised patients with pneumonia can have infection with both common pulmonary pathogens and opportunistic pathogens. A basic microbiological workup should be performed in all immunocompromised patients who are hospitalized and considered for outpatients. The need for a more extensive and invasive workup (eg, bronchoscopy for bronchoalveolar lavage transbronchial lung biopsy) should be individualized, considering risk factors for opportunistic pathogens. As part of treating immunocompromised patients with pneumonia, it is important to evaluate whether any immunosuppressive medications can be discontinued or decreased to improve the patient's level of immunity. Empiric therapy for opportunistic pathogens should be considered in patients who have risk factors for a particular pathogen and when delaying appropriate therapy would increase mortality risk.