The use of fluorescent technologies in neurosurgery has a substantial history with applications to vascular and tumor surgery dating back to the 1940s. This review focuses on the applications of fluorescence imaging to intracranial vascular and neoplastic lesions using sodium fluorescein. The authors performed a literature search for articles about the use of sodium fluorescein in neurosurgery. Fifty-five articles were initially retrieved, and 37 of these were appropriate for this review. The subcategorization of these articles revealed 2 describing the properties of fluorescein, 19 articles relating to applications of fluorescein to tumor, 11 relating to vascular applications, and 5 reporting side effects associated with fluorescein use. Articles related to use of this agent in evaluation of CSF leak were excluded. Sodium fluorescein has been reported to be a useful surgical adjunct in resection of neoplastic lesions based on differential fluorescence between normal and neoplastic tissue. There are many reports on the utility of fluorescein in vascular imaging relating to arteriovenous malformations, aneurysms, and vessel anastomosis; however, these reports do not examine primary outcomes. Sodium fluorescein has been judged as generally safe with few reports of severe complications. Sodium fluorescein has demonstrated promise as a useful surgical adjunct in neurosurgery for vascular and neoplastic lesions. It is well tolerated, but further study is required to determine its full utility. Finally, we will introduce a new practical technology that could potentially improve intraoperative application of sodium fluorescein by improving its fluorescence visualization while using substantially lower doses of this dye.