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Malignant gliomas are associated with poor prognosis. Photodynamic therapy (PDT), relying on light-activated toxicity of a photosensitizer, has been investigated as a means for improving patient survival. This review presents a summary of clinical results obtained with PDT using different photosensitizers for treating brain malignancies. Particular emphasis is on the use of 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX). PpIX is a potent photosensitizer that displays good tumor-selective uptake and characteristic fluorescence. Here, we present clinical data on PpIX biodistribution and PpIX photobleaching kinetics, indicating high tumor selectivity and rapid photobleaching. These data provide the motivation for the use of a dosimetry model aiming at a complete consumption of PpIX during PDT. This dosimetry model, referred to as the advanced photobleaching model, has been implemented for interstitial PDT (iPDT) relying on stereotactic positioning of radial light diffusers within the tumor volume. A summary of preliminary results from our clinical trial on ALA-mediated brain-iPDT is presented. Finally, recent developments of brain-PDT are discussed with respect to their potential to improve treatment efficacy. We have identified individualized dosimetry, the use of multiple photosensitizers and the combination of photosensitizer and immune response modifiers as the most promising strategies for further preclinical and clinical research.