Clinical trials are essential to medical progress because new treatments must be proven safe and effective before they are accepted as standard care. Boron neutron capture therapy (BNCT) is fundamentally different from conventional therapies. The main difference lies in the binary nature of the treatment principle, which requires research into a substance that can attack tumor cells but has no therapeutic effect of its own. Furthermore, not only are the radiation systems and beams used for BNCT significantly different from those used for conventional radiotherapy, but the beams used for BNCT at different centers throughout the world are also different from each other and often need to be approved for patient treatment. Therefore, the development of BNCT as a treatment modality requires strategies that are based on the classical trial design but take into account the challenges and specificities of BNCT. All applicable laws and regulations governing the conduct of clinical trials must be followed. These aspects make BNCT clinical trials a challenging task for clinical investigators and regulatory authorities.