There exists a paucity of structural innovation and limited molecular diversity associated with molecular frameworks in drug discovery and biomolecular imaging/chemical probe design. The discovery and exploitation of new molecular entities for medical and biological applications will necessarily involve voyaging into previously unexplored regions of chemical space. Boron clusters, notably the carboranes, offer an alternative to conventional (poly)cyclic organic frameworks that may address some of the limitations associated with the use of novel molecular frameworks in chemical biology or medicine. The high thermal stability, unique 3D structure and aromaticity, kinetic inertness to metabolism and ability to engage in unusual types of intermolecular interactions, such as dihydrogen bonds, with biological receptors make carboranes exquisite frameworks in the design of probes for chemical biology, novel drug candidates and biomolecular imaging agents. This Review highlights the key developments of carborane derivatives made over the last decade as new design tools in medicinal chemistry and chemical biology, showcasing the versatility of this unique family of boron compounds.