A 55-year-old woman was found unresponsive and subsequently was diagnosed with a subarachnoid hemorrhage secondary to a right posterior communicating artery aneurysm. The development of hydrocephalus and decreased mental status necessitated placement of an intraventricular catheter; 18 days later she was diagnosed with Enterobacter cloacae ventriculitis. After treatment was begun with intravenous cefepime 2 g every 8 hours and intraventricular gentamicin 5 mg every 24 hours, the catheter was replaced. Cerebrospinal fluid (CSF) and plasma cefepime concentrations and a CSF trough gentamicin concentration were obtained. Intraventricular gentamicin was administered for 6 days and cefepime for 21 days; both clinical and microbiologic resolution of the ventriculitis occurred. The literature reports limited clinical experience with cefepime for the treatment of central nervous system infections in humans. This case report provides clinical evidence to support administration of intravenous cefepime in critically ill adult patients with Enterobacter ventriculitis. Because CSF is easily obtained from patients with intraventricular catheters, strong consideration should be given to monitoring CSF cefepime concentrations in concert with the minimum inhibitory concentration of the offending pathogen to help assure the efficacy of this approach to therapy.