Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with neutrons of the appropriate energy to produce high-energy alpha particles and recoiling lithium-7 nuclei. BNCT has been used clinically to treat patients with high-grade gliomas, and a much smaller number with primary and metastatic melanoma. The purpose of this special issue of the Journal of Neuro-Oncology is to provide a critical and realistic assessment of various aspects of basic and clinical BNCT research in order to better understand its present status and future potential. Topics that are covered include neutron sources, tumor-targeted boron delivery agents, brain tumor models to assess therapeutic efficacy, computational dosimetry and treatment planning, results of clinical trails in the United States, Japan and Europe, pharmacokinetic studies of sodium borocaptate and boronophenylalanine (BPA), positron emission tomography imaging of BPA for treatment planning, and finally an overview of the challenges and problems that must be faced if BNCT is to become a useful treatment modality for brain tumors. Clinical studies have demonstrated the safety of BNCT. The next challenge is an unequivocal demonstration of therapeutic efficacy in one or more of the clinical trails that either are in progress or are planned over the next few years.