Gas-containing brain abscess remains a life-threatening disease that requires immediate diagnostic and therapeutic intervention. The aim of this study is to report on a series of gas-containing brain abscess and discuss its pathological mechanism and therapeutic consideration. This study included 11 patients with gas-containing brain abscess at Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan during a 27-year period. The predisposing factors to infection included hematogenous spread in five patients, contiguous infection in one patient, and abnormal fistulous communication due to head injury in four patients. In one patient, the predisposing factor might be contiguous infection from frontal sinusitis or abnormal fistulous communication due to previous sinus surgery. Klebsiella pneumoniae was the most common causative pathogen that was isolated from the gas-containing abscess not related to skull base defect. Among these 11 patients, six underwent excision and five accepted aspiration for the surgical treatment of abscess. In the five patients who underwent aspiration, two required repeated craniotomy to excise the recurrent abscess and repair the abnormal fistulous communication through the skull base. When encountered with a gas-containing abscess in patients with an impaired host defense mechanism, K. pneumoniae infection should be suspected, and further attention should be paid to discovering if other metastatic septic abscesses exist. For patients with a history of basilar skull fracture or surgery involving the skull base, craniotomy is indicated to excise the abscess and repair the potential fistulous communication through the cranium. Aspiration may be a reasonable alternative to treat deep-seated lesions, lesions in an eloquent area, patients with severe concomitant medical disease, or patients without a history of basilar skull fracture or surgery involving the skull base. Prompt diagnosis, appropriate antibiotic use, and meticulous surgical treatment are the only way to obtain a favorable outcome.