Macrophage tracking by magnetic resonance imaging (MRI) with iron oxide nanoparticles has been developed during the last decade for numerous diseases of the CNS. Experimental studies on animal models were confirmed by first clinical applications of MRI technology of brain macrophages for multiple sclerosis, ischemic stroke lesions, and tumors. As activated macrophages act in concert with other immune competent cells, this innovative MRI approach provides new functional data on the immune reaction in these CNS diseases. The MRI detection of brain macrophages defines precise spatial and temporal patterns of macrophage involvement that helps to characterize individual neurological disorders. This approach is being explored as an in vivo marker for the clinical diagnosis of cerebral lesion activity, in experimental models for the prognosis of disease development, and to determine the efficacy of immunomodulatory treatments under clinical evaluation. Comparative brain imaging follow-up studies of blood-brain barrier leakage by MRI with gadolinium-chelates, microglia activation by positron emission tomography with radiotracer ligand PK11195 and MRI detection of macrophage infiltration provide more precise information about the pathophysiological cascade of inflammatory events in cerebral diseases. Such multimodal characterization of the inflammatory events should help in the monitoring of patients, in defining precise time intervals for therapeutic interventions, and in developing and evaluating new therapeutic strategies.