The siliceous sponges, the demosponges and hexactinellid glass sponges, are unique in their ability to form biosilica structures with complex architectures through an enzyme-catalyzed mechanism. The biosilica skeleton of these sponges with its hierarchically structure and exceptional opto-mechanical properties has turned out to be an excellent model for the design of biomimetic nanomaterials with novel property combinations. In addition, biosilica shows morphogenetic activity that offers novel applications in the field of bone tissue engineering and repair. In recent years, much progress has been achieved towards the understanding of the principal enzymes, the silicateins that form the sponge skeletal elements, the spicules, and their self-assembling and structure-guiding properties. The discovery of the silicatein-interacting, scaffolding proteins provided new insights in the mechanism of spiculogenesis. The now available toolbox of enzymes and proteins that are involved in biosilica formation and the biosilica material synthesized by them are of great interest for a variety of applications from nanobiotechnology to nanomedicine.