The dismal clinical results in the treatment of glioblastoma multiforme despite aggressive surgery, conventional radiotherapy, and chemotherapy, either alone or in combination has led to the development of alternative therapeutic modalities. Among these is boron neutron capture therapy (BNCT). This binary system is based upon two key requirements: (1) the development and use of neutron beams from nuclear reactors or other sources with the capability for delivering high fluxes of thermal neutrons at depths sufficient to reach all tumor foci, and (2) the development and synthesis of boron compounds that can penetrate the normal bloodbrain barrier, selectively target neoplastic cells, and persist therein for suitable periods of time prior to irradiation. The earlier clinical failures with BNCT related directly to the lack of tissue penetration by neutron beams and to boron compounds that showed little specificity for and low retention by tumor cells, while attaining high concentrations in blood. Progress has been made both in neutron beam and compound development, but it remains to be determined whether these are sufficient to improve therapeutic outcomes by BNCT in comparison with current therapeutic regimens for the treatment of malignant gliomas.