We report our experience with linezolid in the treatment of 5 patients with central nervous system infections subsequent to neurosurgical interventions. In all cases, initial antimicrobial treatment regimens, including a glycopeptide, either failed or were associated with significant adverse events. The good clinical outcome and the absence of significant side-effects associated with linezolid suggest that it may be an attractive alternative for the treatment of central nervous system infections, particularly in settings characterized by a high incidence of multiresistant Gram-positive pathogens.