It has been estimated that every 1 out of every 5 patients hospitalized for community-acquired pneumonia is immunocompromised. The incidence of critical illness in immunocompromised individuals has risen to comprise fully, a third of all ICU admissions. Increased effectiveness of modern-day immunotherapy for a variety of illnesses has translated into longer survival; therefore, a large population is vulnerable to opportunistic and other infections. Given the breadth of the pathogen spectrum and the difficulties of predicting the pathogen involved, interventions are obviously important in microbiological diagnosis. Nevertheless, since initial antimicrobial therapy is almost always empirical (pending the reports of initial testing), it is necessary to be aware of the predilection that certain immunecompromising conditions have for certain pathogens. This chapter focuses on the approach to a possible infection in individuals such as those living with HIV. It explores the goals and limitations of initial imaging of the lung and attempts to integrate radiographic abnormalities into the diagnostic approach. Microbial pathogens have also been correlated to the type and degree of immune suppression, which is important in guiding the initial therapy of pneumonias, since at the time of presentation, microbiological information is usually not available.