Background: Meningitis is a complex and severe acute infectious disease of the central nervous system and is caused mainly by bacteria and viruses. However, the distinction between aseptic and bacterial meningitis can be difficult for clinicians because the symptoms and the results of laboratory assays are often similar and overlapping, particularly when the use of antibiotics is administered prior to examining the cerebrospinal fluid. Methods: We determined the accuracy of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) for the differential diagnosis between bacterial and aseptic meningitis. A comprehensive search was performed for papers published from January 1989 to July 2013. Prospective or retrospective studies and cerebrospinal fluid (CSF) TNF-α and/or IL-1β cytokine concentrations for differential diagnosis distinguishing bacterial from aseptic meningitis were included. Results: A statistical analysis was performed using Revman and Meta-Disc. This systematic review showed that TNF-α has a sensitivity of 80.5%, specificity of 94.9%, diagnostic odds ratio (DOR) of 71.7, and area under the curve (AUC) = 0.942; IL-1β showed a sensitivity of 86.0%, specificity of 92.3%, DOR of 53.5, and AUC = 0.975. Conclusion: Therefore, TNF-α and IL-1β are useful markers for the prediction of the bacterial meningitis and levels may represent an accurate method that is useful for the differentiation between bacterial and aseptic meningitis.