This Viewpoint describes major advances pertaining to perfunctionalized boron clusters in synthesis and their respective applications. The first portion of this work highlights key synthetic methods, allowing one to access a wide range of polyhedral boranes (B-4 and B-6-B-12 cluster cores) that contain exhaustively functionalized vertices. The second portion of this Viewpoint showcases the historical developments in using these molecules for applications ranging from materials science to medicine. Last, we suggest potential new directions for these clusters as they apply to both synthetic methods and applications.