Beta-2 transferrin is a protein found in cerebral spinal fluid (CSF) and inner ear perilymph, but not in blood, nasal or ear secretions. The purpose of this paper is to evaluate the clinical usefulness of the current assay for beta-2 transferrin for detecting CSF and perilymphatic leaks. We reviewed the hospital records of the first 88 patients having specimens submitted for beta-2 transferrin analysis at our institution. Both CSF and perilymph leaks were identified. However, confirmation of the absence or presence of beta-2 transferrin was directly used in the clinical management of only 55% of the patients. This was largely secondary to the time delay in test processing and initial lack of physician confidence with the test. However, our review of the clinical outcomes relating to the use of the beta-2 transferrin analysis suggests high sensitivity and specificity for the test. Analysis of beta-2 transferrin appears to be a valuable test for detecting CSF leakage and a promising test for confirming perilymphatic leaks. However, to achieve greater clinical usefulness a rapid clinical assay needs to be developed and further information gained regarding the sensitivity and specificity of the beta-2 transferrin assay for detecting CSF and perilymphatic fluid leakage.