External beam boron neutron capture therapy (BNCT) using a reactor has been shown to be effective for the treatment of newly diagnosed glioblastoma multiforme (GBM). To improve clinical results, the optimization of the dosage and of boron delivery agents, the combined use of different boron agents, and the combination of BNCT with other therapeutic modalities have all been studied. Reactor neutron sources are now being overtaken by a move to accelerator-based systems. Despite advances, there is a need for better evidence-based data obtained in randomized trials or by using the prospective case-control method. Furthermore, despite recent improvements in multimodal therapies (e.g., surgery, radiotherapy, chemotherapy, and immunotherapy), GBM easily recurs and continues to have a median overall survival time of <1.5 years. However, there remains a strong rationale for BNCT that it is the only method that can deliver tumor cell-selective high-dose radiotherapy while avoiding radiation damage to the surrounding normal brain tissue for this incurable disease.