Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually:B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount ofB in the tumor but also on the organs at risk. It is not yet possible to determine theB concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure theB concentration in blood and to estimate the boron concentration in tissues based on the assumption that there is a fixed uptake ofB from the blood into tissues. On this imprecise assumption, BNCT can hardly be developed further. A therapeutic approach, combining the boron carrier for therapeutic purposes with an imaging tool, might allow us to determine theB concentration in a specific tissue using a non-invasive method. This review provides an overview of the current clinical protocols and preclinical experiments and results on how innovative drug development for boron delivery systems can also incorporate concurrent imaging. The last section focuses on the importance of proteomics for further optimization of BNCT, a highly precise and personalized therapeutic approach.E.H.-H. and M.K. gratefully acknowledge support from the DFG (HE 1376/38-1); L.S. received funding from GEFLUC Grenoble Dauphiné Savoie