High-grade gliomas represent a widely heterogeneous group of tumors, the most frequent of which is glioblastoma multiforme. Its annual incidence has risen over the last decades, particularly amongst elderly people. The actual standards of care allow for a 15-month median survival rate for WHO grade IV gliomas. As recurrence occurs in more than 85% of patients at the surgical margins, the initial resection extent is a cornerstone of disease control. Fluorescence guided resection (FGR) aims at increasing complete resections and, thus, local control. This technique uses 5-aminolevulinic acid (5-ALA), a natural intermediate substance in the heme-porphyrin biosynthesis pathway, and a protoporphyrin IX (PpIX) precursor. PpIX is fluorescent under blue light exposure. Recent studies reported a significant increase in complete resections using FGR, which were associated with prolonged progression free survival, fewer reinterventions, and delayed neurological deterioration. Here, we depict the principles of this surgical technique, its actual outcomes, and future developments. Lasers Surg. Med. 47:441-451, 2015. (c) 2015 Wiley Periodicals, Inc.