Small, compact, and highly symmetric cube-octameric silsesquioxanes have recently attracted increased attention as scaffolds for tailor-made bioconjugates. The expanded arsenal of effective conjugation methods (CuAAC, TEC, oxime ligation) allows one to decorate these nanoparticles bearing up to eight addressable organic substituents, with a wide range of biorelevant ligands, among them carbohydrates, peptides, miniproteins, reporter molecules, and rare-earth chelates. Low toxicity of COSS-based molecules combined with solubility in aqueous systems and half-life sufficient for in vivo studies make these structures attractive targets for a number of applications, among them drug delivery, tumor diagnostics and therapy.