Surgical removal of tumor mass is a common approach in the management of brain tumors. However, the precise delineation of normal tissue from tumor tissue for a complete resection of tumor mass in brain tumor surgery remains a difficult task for neurosurgeons. Aminolevulinic acid (ALA)-mediated exgogenous fluorescence of protoporphyrin IX (PpIX) is a sensitive approach for tumor imaging. Recent studies suggest that the use of ALA/PpIX-mediated fluorescence-guided resection (FGR) or fluorescence-guided surgery can enable more accurate and complete resection of brain tumors, especially when used in quantitative fashion. This review will highlight the current progress in PpIX-mediated FGR and discuss technical challenges in intraoperative quantification of intracellular PpIX fluorescence during FGR of brain tumor.