The diatom cell is an amazing platform for the bottom-up assembly and functionalization of nanostructured materials with hierarchical structures. This chapter highlights biological and chemical approaches to functionalize nanostructured diatom frustules with metals and metal oxides for optoelectronic device applications, and biomolecules for bionanotechnology applications, particularly biosensing. Diatom frustules possess both photonic and photoluminescent properties. The metabolic insertion of germanium or titanium oxides into the frustule biosilica through diatom cell culture enhances these properties, and imbeds semiconductor nanophases into the frustule structure. Alternatively, solution-based methods conformally deposit metals or metal oxides onto the biosilica surface of nanostructured frustules isolated from diatom cell culture. Application areas include luminescent display materials, photovoltaics, and photocatalysis. The functionalization of nanostructured frustules with antibodies also allows for photoluminescence detection of immunocomplex formation for biosensing applications. Suggested future directions of this rapidly-evolving field include the development of planar diatom frustule biofabrication processes for thin-film devices, as well as the genetic engineering of diatom cells to express functional biomolecules anchored to the frustule biosilica for bionanotechnology applications.