Imaging of infection in the CNS has been handled using cross-sectional imaging for more than two decades now resulting in a large array of descriptive diagnostic criteria, capable, in most circumstances of narrowing the differential diagnosis, detecting life-threatening complications and establishing baseline for assessment of treatment response. Limitations however exist, and in many circumstances, both cross-sectional imaging and nonspecific molecular imaging, such as (18)F-FDG, fail to establish a diagnosis. The availability of pathogen-specific imaging agents/ligands would have a great effect on the management of patients with CNS infection. Besides early diagnosis, avoidance of diagnostic brain biopsies can have significant effect on the mortality and morbidity of patients.