Ventriculitis or post-neurosurgical meningitis or healthcare-associated ventriculitis and meningitis (VM) is a severe infection that complicates central nervous system operations or is related to the use of neurosurgical devices or drainage catheters. It can further deteriorate patients who have already presented significant neurologic injury and is associated with high morbidity, mortality, and poor functional outcome. VM can be difficult to distinguish from aseptic meningitis, inflammation that follows hemorrhagic strokes and neurosurgical operations. The associated microorganisms can be either skin flora or nosocomial pathogens, most commonly, Gram-negative bacteria. Classical microbiology can fail to isolate the culprit pathogen. Novel cerebrospinal fluid (CSF) biomarkers and molecular microbiology can fill the diagnostic gap and expedite pathogen identification and treatment. The pathogens may demonstrate significant resistant patterns and their antibiotic treatment can be difficult, as many important drug classes, including the beta-lactams and the glycopeptides, hardly penetrate to the CSF, and do not achieve therapeutic levels at the site of the infection. Treatment modifications, such as higher daily dose and prolonged or continuous administration, might increase antibiotic levels in the site of infection and facilitate pathogens clearance. However, in the case of therapeutic failure or infection due to difficult-to-treat bacteria, the direct antibiotic instillation into the CSF, in addition to the intravenous antibiotic delivery, may help in the resolution of infection. However, intraventricular antibiotic therapy may result in aseptic meningitis and seizures, concerning the administration of aminoglycosides, polymyxins, and vancomycin. Meanwhile, bacteria form biofilms on the catheter or the device that should routinely be removed. Novel neurosurgical treatment modalities comprise endoscopic evacuation of debris and irrigation of the ventricles. VM prevention includes perioperative antibiotics, antimicrobial impregnated catheters, and the implementation of standardized protocols, regarding catheter insertion and manipulation.