Surgical site infections (SSIs) remain an important cause of morbidity following neurosurgical procedures despite the best medical practices. In addition, hospital infection rates are proposed as a metric for ranking hospitals safety profiles to guide medical consumerism. Recently, the use of topical vancomycin, defined as the application of vancomycin powder directly into the surgical wound, has been described in both cranial and spinal surgeries as a method to reduce SSIs. Early results are promising. Here, we provide a concise primer on the pharmacology, bacterial spectrum, history, and clinical indications of topical vancomycin for the practicing surgeon.