Biomarkers of glial reactivity in Alzheimer’s disease and other neurodegenerative diseases have gained increased attention, highlighting the roles of inflammation, innate immunity, and glial reactivity in disease pathogenesis. Despite the historical focus on Amyloid-β and tau, current research in biomarkers also includes proteins secreted or released by microglia and astrocytes. This chapter focuses on key biomarkers of glial reactivity, specifically sTREM2, progranulin, and Galectin-3 (microglia-related) and GFAP and YKL-40 (astrocyte-related). It highlights the significance of these biomarkers in reflecting specific facets of the glial response, which is dynamic and varies with disease stage, age, and environmental factors. The discussion includes the need for a diverse array of biomarkers to comprehensively characterise glial responses, moving beyond binary classifications. This chapter also explores the potential of PET imaging for visualising glial reactivity. Future research directions emphasise the development of new biomarkers and their combinations, understanding the biological significance of glial markers, and integrating human and animal model data for drug development. The dynamic nature of glial responses, the potential beneficial or detrimental effects of glial reactivity, and the necessity of biomarkers in predicting and monitoring therapeutic responses are underscored. Although glial biomarkers are rarely useful for diagnostic purposes, they hold promise for prognostic and predictive applications in Alzheimer’s disease and neurodegenerative disease treatments and can inform drug development and the identification of novel therapeutic targets.