Pneumocystis jirovecii (PJ), an opportunistic fungus, can have major consequences in terms of morbidity and mortality. These infections occur mainly in immunocompromised patients and are known for their pulmonary tropism (Pneumocystis pneumonia, PCP). While prevention modalities have been studied in HIV-infected populations, evidence is scarce in non-HIV patients. The decision to prescribe prophylaxis for PJ requires assessment of the clinical context, as well as existing risk factors that may predispose an individual to develop PCP. Few indicators exist that are sufficiently sensitive and specific to predict the occurrence of PCP. The decision to use prophylaxis must be made on a case-by-case basis.