Tissue microarrays (TMAs), also known as "tissue chips," are a recently developed method that allows small cores or discs of tissue from dozens or hundreds of (usually paraffin-embedded) specimens to be re-embedded in a tissue block, which can then be further sectioned. The tissue cores can subsequently be studied using any combination of techniques, including immunohistochemistry, in situ hybridization (ISH). fluorescence ISH, and in situ polymerase chain reaction (PCR). To date, the technique has found greatest use in the analysis of neoplasms, including gliomas. We describe, and provide examples of, how TMAs might be utilized in investigation of autopsy (or biopsy) tissues from individuals with non-neoplastic disease, especially to address questions that require systematic review of multiple (nearly) identical brain regions across dozens or hundreds of cases. Specific questions related to patterns of protein expression (e.g. tau, Abeta, alpha-synuclein) in multiple regions of large numbers of brain specimens (from patients with neurodegenerative diseases) can be efficiently examined using TMA technology. One possible use of TMAs in the area of infectious disease might be to examine patterns of HIV-related brain injury or AIDS-related opportunistic CNS infections in the epochs before and after highly active antiretroviral therapy came into widespread use.