Polyhedral oligomeric silsesquioxanes (POSS) are organic-inorganic hybrid molecules piquing the interest of researchers thanks to their synergistic features. The great versatility of POSS nanostructures arises from the easy tunability of peripheral organic moieties combined with the high thermal and chemical stability of the inner inorganic core. In this review, we highlight the use of POSS nanostructures as molecular precursors for the synthesis of homogeneous and heterogeneous catalysts able to promote many processes including alkene epoxidation, C-C bond formation, CO2 conversion, "click reactions", hydrogenation, and ethylene polymerisation, among others. In this scenario, POSS units found application as molecular models for single-site heterogeneous catalysts, stabilising platforms for metal nanoparticles, metal ligands, supports for organic salts, and molecular building blocks for the design of ionic polymers. Herein, we address the catalytic application of POSS nanostructures with the purpose of encouraging the development of performing hybrid catalysts with tailored properties.