Because subdural empyema (SDE) is an unusual central nervous system infection, recognition is not always prompt. Consequent delays can allow a serious but curable infection to become irreparably damaging or even fatal. This condition, particularly in the early stages, is relatively easy to treat. Personal experience with six patients during the past 3 years prompted us to review the data from UCLA and its affiliated hospitals. Among the 23 cases of SDE reviewed, the predisposing factor in 16 was sinusitis, mastoiditis, or otitis media. The clinical presentation, encompassing a systemic febrile illness, headache, and neurological deficit, was monotonously uniform. The high incidence of paranasal sinus involvement in the adult, middle ear infections in infants, and seizures in 15 patients comprised further clinical clues suggesting the diagnosis. Although usually diagnosed as an intracranial inflammatory process, an initial failure to suspect a purulent collection in the subdural compartment was typical. Although the findings of definitive diagnostic studies (computed tomography or angiography) are strikingly positive in advanced cases, in the earlier stages of this disorder they may be subtly abnormal. Because the mortality and morbidity rates, in some measure, depend on the stage at which the process is arrested, the real challenge lies in making a prompt diagnosis. The most favorable results are associated with early, decisive surgical treatment.