Among inorganic nanoparticles, functionalized polyhedral oligomeric silsesquioxanes (POSSs) are unique nano additives that can be used to create a wide variety of hybrid and composite materials, where precise control of nanostructures and properties is required. POSSs have the general formula (RSiO1.5)n, where n is an integer and R can be a large number of substituents including hydrogen, alkyl, aryl, alkenyl, phenyl, halogen and siloxy groups. Incorporation of POSS moieties into polymer matrices influences the mechanical, thermal, physical, rheological and flammability behavior of composites. Different than other nano-additives, POSSs can be chemically bonded with polymer materials during synthesis and even during processing via reactive methods. This keynote presentation covers the applications of POSS nanoparticles in different fields of polymer formulation development, such as crosslinking systems, adhesion enhancer in composites, nano-level reinforcement, compatibilization in blends and etc. The biodegradable and biocompatible polymer formulations are especially highlighted.