Prompt diagnosis and early treatment of cerebrospinal fluid (CSF) leakage minimizes the risk of severe complications. In patients presenting with clear fluid nasal discharge it is important to identify the nature of the rhinorrhea. The CSF leakage may occur as post-traumatic, iatrogenic, spontaneous or idiopathic rhinorrhea. The differential diagnosis of CSF rhinorrhea often presents a challenging problem. The confirmation of CSF rhinorrhea and localization of the leakage may be diagnosed by CT, MRI cisternography and MRI cisternography in combination with single photon emission tomography or radioisotopic imaging. Although these methods allow estimation of the CSF leakage with high accuracy, they are expensive and invasive procedures. Therefore, biochemical methods are still used in the differentiation. Although the most common diagnostic method for screening CSF leakage is glucose oxidase, its diagnostic sensitivity and specificity is generally unsatisfactory. False negative results may occur with bacterial contamination and false positive results are common in diabetic patients. Glucose detection is not recommended as a confirmatory test. As such, other biomarkers of the CSF leakage, such as beta-2-transferrin (beta-2 trf) and beta-trace protein (betaTP) are necessary to identify and confirm of this condition.