Polyhedral oligomeric silsesquioxane (POSS)-dendrimer hybrid materials have attracted great interest in the past ten years. The integration of inorganic POSS and organic dendrimer blocks in a single-phase material offers numerous possibilities to access desirable mechanical, optical, and biomedical properties for various applications. In this review article, we describe several kinds of POSS-dendrimer hybrid materials (POSS as the core, surface functionality, repeating unit of dendrimers and the POSS–dendron conjugates) with an emphasis on their synthetic strategies, tunable macroscopic properties, and potential applications. Moreover, the current trends, challenges and future directions of POSS-dendrimer hybrid materials are elaborated.