The detection of glioblastoma (GBM) in biofluids offers potential advantages over existing paradigms for the diagnosis and therapeutic monitoring of glial tumors. Biofluid-based detection of GBM focuses on detecting tumor-specific biomarkers in the blood and CSF. Current clinical research concentrates on studying 3 distinct tumor-related elements: extracellular macromolecules, extracellular vesicles, and circulating tumor cells. Investigations into these 3 biological classifications span the range of locales for tumor-specific biomarker discovery, and combined, have the potential to significantly impact GBM diagnosis, monitoring for treatment response, and surveillance for recurrence. This review highlights the recent advancements in the development of biomarkers and their efficacy for the detection of GBM.