The development of curative treatment for glioblastoma is extremely challenging. Chemotherapeutic agents that have seemed promising have failed in clinical trials. Drugs that successfully target cancer cells within the brain must first traverse brain interstitial fluid (ISF). Cerebral microdialysis (CMD) is an invasive technique in which ISF can be directly sampled. CMD has been used clinically primarily in the settings of head trauma and subarachnoid hemorrhage. Our goal was to review the techniques, principles and new data pertaining to CMD, highlighting its use in neuro-oncology. We conducted a literature search using the Pubmed database, selecting articles where investigators used CMD either in animal brain tumor models or clinical trials. Bibliographies were reviewed for additional information. Studies of CMD have shown its importance as a neurosurgical technique. CMD allows collection of pharmacokinetic data on drug penetrance across the blood-brain barrier (BBB), and metabolic data characterizing response to chemotherapy. While there have been no reports of complications, current CMD technique (as with any procedure) has risks and limitations, which we describe. Animal CMD experiments have been used to exclude CNS drug candidates from progressing into clinical trials. To date, patients undergoing CMD have been monitored in the ICU, due to the requisite tethering to the apparatus. This is expected to change soon due to advances in micro-miniaturization. CMD is an extremely valuable, yet underutilized technique. Future CMD applications will have central importance in assessing drug delivery to tumor cells in vivo, allowing a pathway to successful therapy for malignant brain tumors.Copyright © 2020 Elsevier Inc. All rights reserved.