Central nervous system (CNS) cancer is a devastating illness with unmet therapeutic needs. Establishing biomarkers that have the potential to guide accurate CNS cancer diagnosis or are helpful in predicting disease progression or therapy response is of great interest. Cerebrospinal fluid (CSF) has been extensively targeted for the detection of molecules that might be useful markers for cancer detection. However, so far very few of such markers have found a standardized routine clinical application. This review examines the current scientific knowledge about the biochemical elements in the CSF that have been reported in the literature as brain cancer biomarkers and highlight reasons why the role of most markers is not yet established in the managment of CNS tumors.