Recently, silsesquioxanes (SSQ) and polyhedral oligomeric silsesquioxanes (POSS) have gained much interest in the area of biomaterials, mainly due to their intrinsic properties such as biocompatibility, complete non-toxicity, the ability to self-assemble and to form a porous structure, facilitating cell proliferation, creating a superhydrophobic surface, osteoinductivity, and ability to bind hydroxyapatite. All the above has resulted in new developments in medicine. However, the application of POSS-containing materials in dentistry is still at initial stage and deserves a systematic description to ensure future development. Significant problems, such as reduction of polymerization shrinkage, water absorption, hydrolysis rate, poor adhesion and strength, unsatisfactory biocompatibility, and corrosion resistance of dental alloys, can be addressed by the design of multifunctional POSS-containing materials. Because of the presence of silsesquioxanes, it is possible to obtain smart materials that allow the stimulation of phosphates deposition and repairing of micro-cracks in dental fillings. Hybrid composites result in materials exhibiting shape memory, as well as antibacterial, self-cleaning, and self-healing properties. Moreover, introducing POSS into polymer matrix allows for materials for bone reconstruction, and wound healing. This review covers the recent developments in the field of POSS application in dental materials and gives the future perspectives within a promising field of biomedical material science and chemical engineering.