Immunohistochemistry has revolutionized both the research and diagnostic endeavors of anatomic and surgical pathologists, including neuropathologists. These methods, which use the high specificity of antibody recognition of target antigens, have largely replaced the more capricious, less sensitive, and less specific panoply of metallic impregnations and other histochemical methods that once were characteristics of neuropathology. With immunostaining, specific infectious agents, from ordinary bacteria to spirochetes, fungi, parasites, and especially viruses, can be identified as the causative agents of central nervous system diseases. Understanding of the pathogenesis and establishment of correct diagnoses of neurodegenerative disorders are both improved, and more precise and reliable diagnosis of central nervous system tumors has become a matter of immunophenotypic characterization using panels of relevant antibodies to supplement the recognition of standard histologic patterns. Newer trends in neuropathologic immunohistochemistry point to a better understanding of the molecular pathology of degenerative disorders and of tumors as specifically mutated oncogenetic or neurotoxic antigens are localized and identified in diseased brain and spinal cord tissues.