Temozolomide is an FDA approved oral alkylating agent used in newly diagnosed and recurrent high grade gliomas. While temozolomide with radiotherapy has modestly improved overall survival rates in high grade gliomas, previous studies have proven that levels of temozolomide in the brain are only 20% of systemic drug levels [26, 27]. The peak concentration of temozolomide in the brain occurs approximately 1–2 h after ingestion. Once ingested, temozolomide undergoes degradation from its prodrug form to the highly reactive alkylating agent, methyl-triazenyl imidazole carboxamide (MTIC). Previous studies have utilized CSF sampling and intracerebral microdialysis catheters (MDC) to measure temozolomide brain extracellular concentrations in primary or metastatic brain tumors. Use of an indwelling MDC for long term tissue monitoring in the cerebrum is not new, and this technique has been utilized mainly in the traumatic brain injury setting. Prolonged catheter placement allows for continued fluid collections in alert and mobile patients [28–30]. These catheters are often placed in the operating room with verification of placement determined by brain CT. The presence of a gold filament at the catheter tip allows for easy visibility on non-contrast CT brain imaging. The semi-permeable catheter performs similarly to a capillary when perfusion fluid is pumped continuously through it. The presence of the microvial at the end of the catheter allows for regular interval sampling of the dialysate fluid. Then, drug recovery is assessed in each dialysate sample as an indirect measurement of free drug concentration.