In patients with immunodeficiency the pathogen spectrum of central nervous system (CNS) infections is broader and different from that of immunocompetent patients. Numerous opportunistic infections are characterized by a high prevalence of viral, bacterial and parasitic pathogens, and depend on the type of impaired immune defense, for example impaired T‑cell or monocyte function, monoclonal antibody treatment, and impaired granulocyte function. Neuroradiological features as well as laboratory findings are often different and versatile in comparison to immunocompetent individuals and pathognomonic imaging findings do not exist; however, knowledge of possible pathways of pathogens in the CNS and preferred tissue affection may help in narrowing down differential diagnoses. Therefore, knowledge of the type of patient and the performed immunomodulatory therapy is essential for the neuroradiological assessment and the differential diagnostic considerations. Moreover, parenchymal reactions in the sense of an immune reconstitution inflammatory syndrome (IRIS) can occur when immunocompetence is restored. This review focus on the most common pathologies in immunocompromised patients, and an overview of imaging features but also of pathology and clinical aspects is given. The synopsis of anamnestic information, clinical findings and structured analysis of the lesion pattern, its spread and short-term follow-up may increase the correct diagnostic classification; however, the gold standard is still determination of the pathogen in the cerebrospinal fluid (CSF), blood cultures or biopsies.