The application of organic polymers and inorganic/organic hybrid systems in numerous fields of biotechnology has seen a considerable growth in recent years. Typically, organic polymers with diverse structures, compositional variations and differing molecular weights have been utilized to assemble polymeric nanosystems such as polymeric micelles, polymersomes, and nanohydrogels with unique features and structural properties. The architecture of these polymeric nanosystems involves the use of both hydrophobic and hydrophilic polymeric blocks, making them suitable as vehicles for diagnostic and therapeutic applications. Recently, “smart” or “intelligent” polymers have attracted significant attention in the biomedical field wherein careful introduction of specific polymeric modalities changes a banal polymeric nanosystem to an advanced stimuli-responsive nanosystem capable of performing extraordinary functions in response to an internal or external trigger such as pH, temperature, redox, enzymes, light, magnetic, or ultrasound. Further, incorporation of inorganic nanoparticles such as gold, silica, or iron oxide with surface-bound stimuli-responsive polymers offers additional advantages and multifunctionality in the field of nanomedicine. This review covers the physical properties and applications of both organic and organic/inorganic hybrid nanosystems with specific recent breakthroughs in drug delivery, imaging, tissue engineering, and separations and provides a brief discussion on the future direction.