Both the safety and effectiveness of intrathecal tigecycline (TGC) for treatment of infections of the central nervous system (CNS) are discussed using the clinical findings from a study of a recent patient who came to our attention, along with a literature review. Although penetration into the CNS is low (approximately 11%), intraventricular TGC could help treat patients with severe post- neurosurgical CNS infections. The use of multiple routes of TGC administration appears to be encouraging and should be considered in managing life-threatening intraventricular infections.