Guidelines for administration of vancomycin into the cerebrospinal fluid are not available, and dosing strategies are based off of case reports and small clinical trials, with most data published before 2005. The objective of this article was to review available literature on direct administration of vancomycin into the cerebrospinal fluid for treatment of central nervous system–related infections and to determine current best therapeutic practice in dosing vancomycin by intrathecal or intraventricular administration. Upon literature review, cited initial vancomycin doses ranged from 5 to 50 mg/d. Maintenance dosing strategies tended to fall between 5 and 10 mg/d to maintain goal trough levels of 5 to 15 µg/mL. Therapeutic monitoring was a consistent recommendation made by authors to maintain therapeutic levels as well as to avoid possible toxicities associated with intraventricular and intrathecal vancomycin administration. Toxicities were limited in review but included mental status changes and headaches.