Since Locher proposed the concept of boron neutron capture therapy (BNCT) in 1936, it has become a great challenge in the field of medicinal chemistry. The great dare has been to obtain boron-containing compounds that selectively accumulate in the organ to be irradiated. Polyhedral boron clusters (PBC) have been considered attractive moieties for the development of BNCT-agents due to their large contribution of boron per molecule. Various issues arose in the first efforts to develop PBC during the 1940-1950s that prevented their application in BNCT clinical trials, such as a lack of selectivity and low boron tumor-accumulation. Currently, the most studied PBC in BNCT are the icosahedral dicarba-closo-dodecaboranes (C2B10H12) commonly referred to carboranes and, to a lesser extent, their mono-anionic derivatives resulting from the loss of a B-vertex, commonly known as nido-carborane, and their metal complexes, known as metallacarboranes. This review will cover the medicinal chemistry of PBC for BNCT.