Silsesquioxanes (SSQs) comprise an interesting and versatile class of three-dimensional organosilicate oligomers with diverse structural arrangements and interesting physicochemical properties. SSQs are of considerable technological interest, with applications that include the development of electrochemical detection devices. The presence of functional groups on their structures enables the anchoring of different electroactive and conductive species, such as complexes, metal nanoparticles and carbon nanomaterials, and biomolecules, including enzymes, nucleic acids, and antibodies, which boosts the sensitivity and selectivity of the obtained (bio)sensors. These materials can also be incorporated into conductive matrices using a range of methods, which enhances their versatility. This mini review provides an overview of the most recent applications of hybrid organic–inorganic SSQs in the preparation of modified electrodes for the development of electrochemical sensors and biosensors. Special focus is placed on the incorporation of nanomaterials in their polymeric structure and on the design and fabrication of electrochemical devices using different strategies.