Brain biopsies aim at obtaining a diagnosis through histopathological examination in order to guide therapeutic decision. Beyond the examination of standard staining, a wide range of analytical methods is available in neuropathology from special stainings to immunohistochemistry and molecular biology. As the amount of tissue is limited, an appropriate management of the biopsy sample is pivotal to achieve a comprehensive diagnosis with relevant tests and biomarkers. This chapter addresses practical procedures to adapt the management of brain biopsy samples to a given clinical context and to optimize tissue for additional uses including immunohistochemistry, molecular analyses of tumors, and metagenomics of infectious diseases. The role of tissue freezing and biobanking in care and research is highlighted.