Boron neutron capture therapy (BNCT) is a unique method that can deliver tumor-cell-selective high-linear energy transfer (LET) particle radiotherapy to an extended target area encompassing a microscopic invasion while avoiding radiation damage to the surrounding normal brain tissue. The process of BNCT is based on the nuclear interaction of 10B with thermal neutrons with the release of high LET α and 7Li particles through the boron neutron capture reaction, 10B(n, α) 7Li. The very short path length (<9 μm) of α-particles and 7Li enables high-LET irradiation of tumor cells without undesirable damage to 10B-unloaded normal cells. Eight non-randomized prospective external beam BNCT trials for glioblastoma (GBM) have been performed over 15 years using the two currently available boron drugs and a neutron beam at a nuclear reactor. Four of the 8 studies suggested that the external beam BNCT may improve survival in newly diagnosed GBM. In addition, 4 of the 8 studies were primary phase I trials that demonstrated only modest toxicity. The median time to progression and the median survival time (MST) were 6–12 months and 12–27 months, respectively. The optimization of dosage and boron delivery agents, the combined use of different boron agents, the combination of BNCT with other therapeutic modalities and the development of a hospital-based neutron source have been studied for the improvement of BNCT. The need for more evidence-based data, either through randomized trials or using a prospective case control methodology, is clear from a review of the clinical reports.