The study of the pathology of the nervous system involves different techniques, which are used to obtain the material for study and diagnosis. These include stereotactic biopsies of small or inaccessible lesions, trephine biopsies at the time of surgery and larger formal biopsies of lesions, including excisions. Some disease such as encephalitis may involve obtaining random biopsies; intractable epileptiform disorders may have to be treated by removal of a lobe or more of the brain. Tissue can be studied by cytologic preparations obtained by brain (tumor/lesion) squash (crush preparations) techniques, by a frozen section or after more formal processing, paraffin embedding and sectioning. In the past celloidin (sulfated and nitrated cellulose) impregnation and sectioning was used to obtain whole slices of brain, to study the submacroscopy of pathologic processes. With the advent of stereotactic biopsies the amount of material available is limited and one has to use cytologic techniques alone or in combination with frozen sections. Sometimes it is prudent to reserve tissue for formal processing and paraffin sections, to better appreciate the pathology. The initial impressions, based on smears or frozen sections will prompt the pathologist to keep tissue aside for electron microscopy, microbial culture or other studies. The recent American College of Pathology guidelines have addressed the issue of prioritizing the method of evaluating small biopsies; brain squash preparations are followed by paraffin sections, and then come frozen sections and finally Electron Microscopy (EM), etc. The study is extendable to the study of the cerebrospinal fluid (CSF) and its cellular and noncellular contents. CSF cytology has become the standard to determine the involvement of the nervous system in diseases such as lymphoproliferative disorders. With the use of immunostains and flow cytometry on cells from the CSF, an accurate and specific diagnosis is possible in many cases where involvement is present. A neurosurgeon’s understanding of neuropathology has to be relevant to his practice, and pertains, for the most part, to mass forming lesions. They, however, have to be familiar with tumor mimics such as demyelinating pseudotumors of the nervous system. With the changing spectrum of disease and new modalities of treatment, there is now a requirement of biopsy diagnosis of infective lesions encountered in the setting of immunosuppression and for the biopsy diagnosis of tumors, which will be treated by nonsurgical techniques. This review has therefore a bias towards neurosurgical pathology material, rather than conventional neuropathology. The advances in radiology make imaging an intrinsic part of the diagnostic pathology armamentarium, and hence some emphasis has been given to this also, though details will be found elsewhere.